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Platelet Transfusion for Treatment of Patent Ductus Arteriosus in Thrombocytopenic Preterm Neonates

Primary Purpose

Patent Ductus Arteriosus

Status
Completed
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Liberal platelet transfusion
Restrictive platelet transfusion
Paracetamol
Ibuprofen
Sponsored by
Postgraduate Institute of Medical Education and Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Patent Ductus Arteriosus focused on measuring PDA, Platelets

Eligibility Criteria

1 Day - 14 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Gestational age up to 34 6/7 weeks
  2. PDA detected for the first time at less than 14 days of postnatal age
  3. Clinically and/or echocardiographically hemodynamically significant PDA Note: ELBW neonates will be screened in first 48 hours as per unit policy; the rest will undergo echocardiography only when there are clinical signs of PDA.
  4. Platelet count within 24 hours prior to inclusion is less than 100,000 per microliter.

Note: If a platelet count is already available within 24 hours prior to inclusion it will be accepted as a valid platelet count. If not, an urgent absolute platelet count will be performed.

Exclusion Criteria:

  1. Echocardiographically proven structural congenital heart disease.
  2. Major life-threatening malformation
  3. Received platelet concentrate between the last available platelet count and the point of randomisation

Sites / Locations

  • Post Graduate Institute of Medical Education and Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Liberal Platelet transfusion group

Restrictive platelet transfusion group

Arm Description

Platelet transfusion to maintain a platelet count above 1,00,000 per microliter until one of the endpoints is met. As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician: Ibuprofen: Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral Paracetamol: Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV

Platelet transfusion for standard criteria. As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician: Ibuprofen: Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral Paracetamol: Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV

Outcomes

Primary Outcome Measures

Time to closure of PDA post randomization
Time point at which closure (Absence of flow in PDA on colour doppler) is documented first time will be considered as time to closure of PDA

Secondary Outcome Measures

Proportion of participants in whom PDA is open
PDA will be considered open if there is presence of flow on colour doppler
Proportion of participants in whom PDA is echocardiographically hemodynamically significant
hemodynamic significance is defined somewhere else in text
Cumulative volume of platelet concentrate received
Total volume in ml/kg will be recorded
Number of participants with Clinical bleed of any kind ( defined below)
Any visible fresh oral, nasal, endotracheal, gastrointestinal or skin bleed will be considered as clinical bleed.
New onset IVH of any grade
Cranial ultrasound will be done as per protocol to look for IVH
New onset IVH of grade 3or 4
Cranial ultrasound will be done as per protocol to look for IVH
Mortality
It stands for all cause mortality
Mortality
It stands for all cause mortality
Duration of hospital stay
Duration of stay will be from date of birth to date of discharge/referral or death
Reopening rate of PDA that had initially closed
It will include situation where PDA closure was documented on two consecutive occasions 24 hours apart and then at later stage it opens.

Full Information

First Posted
June 25, 2016
Last Updated
April 5, 2018
Sponsor
Postgraduate Institute of Medical Education and Research
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1. Study Identification

Unique Protocol Identification Number
NCT03022253
Brief Title
Platelet Transfusion for Treatment of Patent Ductus Arteriosus in Thrombocytopenic Preterm Neonates
Official Title
Liberal Versus Restrictive Platelet Transfusion for Treatment of Hemodynamically Significant Patent Ductus Arteriosus in Thrombocytopenic Preterm Neonates- A Randomized Open Label, Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
March 2016 (undefined)
Primary Completion Date
March 20, 2017 (Actual)
Study Completion Date
March 20, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Postgraduate Institute of Medical Education and Research

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Patent ductus arteriosus (PDA) is a common problem in preterm babies. Recently there have been various studies for and against an association between thrombocytopenia and PDA. A meta-analysis published in 2015 showed a marginally significant positive association between PDA and thrombocytopenia but these were all observational studies and there are no randomized controlled trials (RCT) on it. The investigators decided to conduct an RCT to determine whether liberal platelet transfusion criteria achieve earlier PDA closure rates than standard restrictive platelet transfusion criteria among thrombocytopenic preterm neonates (<35 weeks' gestation) with hemodynamically significant PDA presenting within the first 14 days of life. The investigators primary objective is to determine whether liberal platelet transfusion criteria achieve earlier PDA closure rates within 120 hours compared to standard restrictive platelet transfusion criteria among thrombocytopenic preterm neonates (<35 weeks' gestation) with hemodynamically significant PDA presenting within the first 14 days of life. The investigators will stratify the study population based on platelet count, i.e < 50000 and 50000-100000 per microlitre, and will randomly allocate participants to control and intervention group. Babies in the intervention group will receive platelet transfusion to maintain the platelet count above 100,000 per microlitre. Babies in control group will receive platelets only when clinically indicated and as per current standard indications. The investigators will perform an echocardiogram at baseline to document a hemodynamically significant PDA (hsPDA) and then serially to look for the closure of PDA. Medical management of PDA will be as per unit policy. The investigators will follow the baby till PDA closes or 120 hours post randomization.
Detailed Description
Study Background: Preterm babies are a unique group of patients in Newborn Intensive Care Unit. Patent ductus arteriosus (PDA) is a common complication related to the gestational age of preterm birth. In infants born at less than 32 weeks of gestation, the frequency of PDA has been reported from 50% to 80%. Physiologic ductus arteriosus closure occurs in the first 3 days after birth. The persistence of a PDA beyond the first postnatal days of life, however, is frequently associated with multiple severe complications, predominantly in the most immature infants It is currently believed that ductus arteriosus (DA) closure involves a two-step process. The first, 'provisional' closure is accomplished by smooth muscle cell contraction and ductus arteriosus (DA) constriction. Subsequently, the proliferation of cells within the former DA lumen leads to anatomical remodeling of the DA and permits permanent closure. Recently an association between the absolute platelet count and the closure of ductus arteriosus has been the focus of research. Various prospective and retrospective studies have been conducted for the same. In 2015 systematic review and meta-analysis by Sorina et al showed a significant positive association between PDA and thrombocytopenia. Hence the investigators planned randomized controlled trial to look for the effect of platelet transfusion on closure rates of ductus arteriosus. Research question: Do liberal platelet transfusion criteria achieve earlier PDA closure rates than standard restrictive platelet transfusion criteria among thrombocytopenic preterm neonates (<35 weeks gestation) with hemodynamically significant PDA presenting within the first 14 days of life? Objectives: Primary objective: To determine whether liberal platelet transfusion criteria achieve earlier PDA closure rates within 120 hours compared to standard restrictive platelet transfusion criteria among thrombocytopenic preterm neonates (<35 weeks gestation) with hemodynamically significant PDA presenting within the first 14 days of life. Secondary objectives: To determine the time period between platelet transfusion and closure of PDA. To compare between the 2 groups: Proportion in whom PDA is open at 24 hours after the last dose of the course of medication Proportion in whom PDA is echocardiographically hemodynamically significant at 24 hours after the last dose of the course of medication Proportion in whom PDA is echocardiographically hemodynamically significant at 120 hours after randomization Cumulative volume of platelet concentrate received within 120 hours after randomization Any kind of clinical bleed within 120 hours after randomization New onset Intraventricular hemorrhage (IVH) of any grade within 120 hours after randomization New onset IVH of grade 3,4 within 120 hours after randomization Mortality within 120 hours after randomization Mortality anytime during hospital stay Duration of hospital stay Reopening rate of PDA that had initially closed within 120 hours of randomization Study Design: This will be a randomized, open-label, controlled trial. Place of study Newborn unit of the Department of Pediatrics Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India Study period: Subject recruitment and data collection: January 2016 to December 2016 (12 months) Data analysis: January 2017 to March 2017 (3 months) Writing of dissertation: April 2017 to June 2017 (3 months) Screening criteria (all must be fulfilled): The investigators will screen all inborn and outborn neonates (admitted in Neonatal intensive care unit (NICU) or Neonatal nursery (NNN) for the following: Gestational age up to 346/7 weeks PDA detected for the first time at less than 14 days of postnatal age Infants who meet the screening criteria will undergo an echocardiogram conducted by the 1st investigator and a platelet count and will be included if they fulfill all the following inclusion criteria mentioned below. Procedure of platelet count: The investigators will draw 0.5 ml of blood into an Ethylene diamine tetraacetic acid (EDTA) Container and immediately send it for analysis to the emergency lab Room No. 24 situated in Advanced Trauma Centre PGIMER Chandigarh. A technician will measure the platelet count by using an automated blood cell coulter (Sysmex KX-21 Coulter) situated in this lab. One of the co-investigators (N.V.) will ensure that the facility of platelet counts is available round-the-clock within a turnaround time of about 2 hours for subjects enrolled in the trial, and will also ensure quality control of the procedure. Procedure of echocardiography: The first investigator (JK) will perform the echocardiogram on a SonoSite MicroMaxx Portable Ultrasound Machine. Extremely low birth neonates (ELBW) neonates will be screened in first 48 hours as per unit policy, and the rest will undergo echocardiography only when there are clinical signs of PDA. Before performing the echocardiogram, the first investigator will use a website-generated unique, random code number as the patient identifier. The first investigator will take a backup of each echocardiogram immediately on an external hard drive and the video files will be named with the same website-generated random code number. One of the co-investigators (VS or SS) will review the code numbered echocardiograms. VS and SS will be masked to the identity and clinical details of the patients. The key to the code numbers will be maintained by JK and Sourabh Dutta (SD). The echocardiographic diagnosis of PDA by VS or SS will be considered to be the gold standard. The following information will be recorded for each echocardiogram: Whether the ductus arteriosus is patent or closed. If it is patent, Transductal diameter, Ductal velocity, Antegrade left PA diastolic flow, Left Atrium/Aorta (LA/Ao) ratio, E/A, Isovolumic relaxation time (IVRT) , Absent or reversed diastolic blood flow pattern in descending thoracic aorta. Patient information and informed consent: The 1st investigator (J.K.) will approach parents of subjects that meet the above eligibility criteria for possible enrollment in the study. The first investigator will provide them a detailed information sheet and also give a verbal explanation about the study. The first investigator will enroll neonates only after obtaining written informed consent from one of the parents. Baseline data: The investigators will record baseline maternal and neonatal data. Medical treatment of PDA: As all subjects recruited in the trial will have hemodynamically significant PDA, they will all be medically treated. Details are given under intervention heading. Some subjects may be recruited in another ongoing RCT during the initial months of this trial. The other RCT compares paracetamol and ibuprofen in a blinded fashion amongst subjects with hemodynamically significant PDA for the closure of PDA. For such subjects, the trial drug regime will be followed. The index trial will not be affected by being co-recruited in the other ongoing RCT. If a particular dose of medication cannot be given because of a contraindication (an adverse effect or adverse clinical condition) that arises during the course of treatment, that dose will be deferred until it is safe to administer the dose. The duration of medical treatment will be taken as the total duration inclusive of the deferred dose/s. Randomization: The investigators will allocate patients according to a stratified, block randomised design. The investigators will stratify patients into the following strata: a) platelet count < 50,000 per microliter b) platelet count 50,000-100,000 per microliter. The Chief guide Sourabh Dutta (S.D.) will generate the randomisation sequence and construct randomly varying, permuted, even-numbered blocks for each stratum. The chief guide will conceal the block sizes until the end of the study. Each stratum will have its independent randomisation sequence. After the 1st investigator identifies the stratum, S.D. will randomly allocate subjects to an intervention or control group. The investigators will ensure concealment of allocation by using serially numbered opaque sealed envelopes which will bear a slip of paper with the allocation group. Allocation groups: Intervention group: The investigators will transfuse platelet concentrates to maintain platelet count above 1, 00,000 per microliter (details are given under Arms and Intervention) The investigators will aggressively monitor platelet counts in the intervention group, depending upon the stratum in which the subject is enrolled. In the stratum that has a baseline platelet count less than 50,000 per microliter, there is very little chance that the platelet count will rise to more than 100,000 per microliter with a single platelet concentrate transfusion. In this stratum, two back to back platelet concentrates (20 ml/kg each) will be transfused without performing a platelet count in between the 2 tests transfusions. In the stratum that has a baseline platelet count from 50,000 to 100,000 per microliter, a platelet count will be performed after a single transfusion. In both strata, platelet count will be repeated in a window period of 2 hours after the end of the platelet transfusion. The investigators will attempt to club this platelet count with another blood sampling for clinical indications if possible. The investigators will attempt to get the post-transfusion platelet count within a turnaround time of 2 hours. If the subject has a platelet count less than 100,000 per microliter, the investigators will repeat a platelet transfusion, and so on, subject to a maximum volume of 40 ml/kg/day of platelet concentrates in a 24-hour period (defined as 8 AM to 8 AM next day). The investigators will temporarily stop transfusing platelet concentrates once the investigators get a value of above 100,000 per microliter. In addition to the platelet counts performed post-transfusion, the investigators will also perform platelet counts for the following indications: (i) Clinical bleeds (ii) A routine platelet count once in every 24 hours until PDA closes or the criterion of 120 hours post randomization is met. The platelet count for clinical bleeds and routine platelet counts will not be repeated in case a platelet count post-transfusion is already available within a window period of 4 hours prior. Control group: (details are given under Arms and Intervention) In the control group, the investigators will perform platelet counts as per the standard unit practices. A platelet count will be repeated whenever the subject is next sampled for a clinical indication or a longer with routine samples in the evening or morning. A platelet transfusion will be repeated if the platelet count falls to less than 20,000 per microliter or if any of the above criteria are met. In both groups, platelet concentrates will be transfused according to platelet count prior to transfusion. In babies with platelet count < 50000, 50-75000 and 75-1, 00, 00 per microliter the investigators will transfuse @ 20, 15 and 10 ml/kg/transfusion respectively up to a maximum of 40 ml/kg/day. The investigators will administer injection furosemide 0.5 mg/kg as slow IV injection midway through the transfusion if the treating team clinically feels that the patient is likely to develop congestive cardiac failure or pulmonary edema. Study endpoints: Subjects will be followed up in the study until the earliest among Withdrawal of consent Discharge from hospital Death

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patent Ductus Arteriosus
Keywords
PDA, Platelets

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Liberal Platelet transfusion group
Arm Type
Experimental
Arm Description
Platelet transfusion to maintain a platelet count above 1,00,000 per microliter until one of the endpoints is met. As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician: Ibuprofen: Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral Paracetamol: Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV
Arm Title
Restrictive platelet transfusion group
Arm Type
Active Comparator
Arm Description
Platelet transfusion for standard criteria. As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician: Ibuprofen: Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral Paracetamol: Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV
Intervention Type
Biological
Intervention Name(s)
Liberal platelet transfusion
Intervention Description
Liberal platelet transfusion: In Intervention group the investigators will transfuse platelet concentrates to maintain a platelet count above 1,00,000 per microliter until one of the following endpoints is met, whichever is applicable: PDA closes or A maximum of 120 hours after the point of randomisation
Intervention Type
Biological
Intervention Name(s)
Restrictive platelet transfusion
Intervention Description
The investigators will transfuse platelets only if: (i) Platelet count is < 20,000 per microliter or (ii) Subject has a clinical bleed or (iii) Subject has platelet count < 50000 per microliter and requires a major non-neurosurgical interventional procedure as per the current standard of care, or (iv) Subject has a platelet count < 1, 00,000 per microliter and requires a neurosurgical procedure
Intervention Type
Drug
Intervention Name(s)
Paracetamol
Other Intervention Name(s)
Crocin
Intervention Description
As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician: Paracetamol: Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Other Intervention Name(s)
Brufen
Intervention Description
As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician: Ibuprofen: Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral
Primary Outcome Measure Information:
Title
Time to closure of PDA post randomization
Description
Time point at which closure (Absence of flow in PDA on colour doppler) is documented first time will be considered as time to closure of PDA
Time Frame
within 120 hours post randomisation
Secondary Outcome Measure Information:
Title
Proportion of participants in whom PDA is open
Description
PDA will be considered open if there is presence of flow on colour doppler
Time Frame
at 120 hours after randomization
Title
Proportion of participants in whom PDA is echocardiographically hemodynamically significant
Description
hemodynamic significance is defined somewhere else in text
Time Frame
at 120 hours after randomization
Title
Cumulative volume of platelet concentrate received
Description
Total volume in ml/kg will be recorded
Time Frame
within 120 hours after randomization
Title
Number of participants with Clinical bleed of any kind ( defined below)
Description
Any visible fresh oral, nasal, endotracheal, gastrointestinal or skin bleed will be considered as clinical bleed.
Time Frame
within 120 hours after randomization
Title
New onset IVH of any grade
Description
Cranial ultrasound will be done as per protocol to look for IVH
Time Frame
within 120 hours after randomization
Title
New onset IVH of grade 3or 4
Description
Cranial ultrasound will be done as per protocol to look for IVH
Time Frame
within 120 hours after randomization
Title
Mortality
Description
It stands for all cause mortality
Time Frame
within 120 hours after randomization
Title
Mortality
Description
It stands for all cause mortality
Time Frame
All subjects will be part of the study until death or discharge from the hospital. Timeframe for measuring mortality as an outcome is from the point of randomisation through the study period which will be approximately upto 30 days post randomisation
Title
Duration of hospital stay
Description
Duration of stay will be from date of birth to date of discharge/referral or death
Time Frame
All subjects will be part of the study until death or discharge from the hospital.Timeframe for measuring duration of hospital stay is from the point of randomisation through the study period which will be approximately upto 30 days post randomisation
Title
Reopening rate of PDA that had initially closed
Description
It will include situation where PDA closure was documented on two consecutive occasions 24 hours apart and then at later stage it opens.
Time Frame
within 120 hours of randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
14 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Gestational age up to 34 6/7 weeks PDA detected for the first time at less than 14 days of postnatal age Clinically and/or echocardiographically hemodynamically significant PDA Note: ELBW neonates will be screened in first 48 hours as per unit policy; the rest will undergo echocardiography only when there are clinical signs of PDA. Platelet count within 24 hours prior to inclusion is less than 100,000 per microliter. Note: If a platelet count is already available within 24 hours prior to inclusion it will be accepted as a valid platelet count. If not, an urgent absolute platelet count will be performed. Exclusion Criteria: Echocardiographically proven structural congenital heart disease. Major life-threatening malformation Received platelet concentrate between the last available platelet count and the point of randomisation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sourabh Dutta, MD
Organizational Affiliation
Post Graduate Institute of Medical Education and Research; Chandigarh, India
Official's Role
Study Director
Facility Information:
Facility Name
Post Graduate Institute of Medical Education and Research
City
Chandigarh
ZIP/Postal Code
160012
Country
India

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16210841
Citation
Bancalari E, Claure N, Gonzalez A. Patent ductus arteriosus and respiratory outcome in premature infants. Biol Neonate. 2005;88(3):192-201. doi: 10.1159/000087582.
Results Reference
background
PubMed Identifier
20732945
Citation
Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Schibler K, Carlo WA, Kennedy KA, Poindexter BB, Finer NN, Ehrenkranz RA, Duara S, Sanchez PJ, O'Shea TM, Goldberg RN, Van Meurs KP, Faix RG, Phelps DL, Frantz ID 3rd, Watterberg KL, Saha S, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010 Sep;126(3):443-56. doi: 10.1542/peds.2009-2959. Epub 2010 Aug 23.
Results Reference
background
PubMed Identifier
22284694
Citation
Adrouche-Amrani L, Green RS, Gluck KM, Lin J. Failure of a repeat course of cyclooxygenase inhibitor to close a PDA is a risk factor for developing chronic lung disease in ELBW infants. BMC Pediatr. 2012 Jan 27;12:10. doi: 10.1186/1471-2431-12-10.
Results Reference
background
PubMed Identifier
19966813
Citation
Echtler K, Stark K, Lorenz M, Kerstan S, Walch A, Jennen L, Rudelius M, Seidl S, Kremmer E, Emambokus NR, von Bruehl ML, Frampton J, Isermann B, Genzel-Boroviczeny O, Schreiber C, Mehilli J, Kastrati A, Schwaiger M, Shivdasani RA, Massberg S. Platelets contribute to postnatal occlusion of the ductus arteriosus. Nat Med. 2010 Jan;16(1):75-82. doi: 10.1038/nm.2060. Epub 2009 Dec 6.
Results Reference
background
PubMed Identifier
26159239
Citation
Simon SR, van Zogchel L, Bas-Suarez MP, Cavallaro G, Clyman RI, Villamor E. Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis. Neonatology. 2015;108(2):143-51. doi: 10.1159/000431281. Epub 2015 Jul 7.
Results Reference
background
PubMed Identifier
23519783
Citation
Stoller JZ, Demauro SB, Dagle JM, Reese J. Current Perspectives on Pathobiology of the Ductus Arteriosus. J Clin Exp Cardiolog. 2012 Jun 15;8(1):S8-001. doi: 10.4172/2155-9880.S8-001.
Results Reference
background
PubMed Identifier
11158594
Citation
Loftin CD, Trivedi DB, Tiano HF, Clark JA, Lee CA, Epstein JA, Morham SG, Breyer MD, Nguyen M, Hawkins BM, Goulet JL, Smithies O, Koller BH, Langenbach R. Failure of ductus arteriosus closure and remodeling in neonatal mice deficient in cyclooxygenase-1 and cyclooxygenase-2. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1059-64. doi: 10.1073/pnas.98.3.1059. Epub 2001 Jan 23.
Results Reference
background
PubMed Identifier
17164135
Citation
Yu Y, Funk CD. A novel genetic model of selective COX-2 inhibition: comparison with COX-2 null mice. Prostaglandins Other Lipid Mediat. 2007 Jan;82(1-4):77-84. doi: 10.1016/j.prostaglandins.2006.05.021. Epub 2006 Jul 7.
Results Reference
background
PubMed Identifier
10944235
Citation
Reese J, Paria BC, Brown N, Zhao X, Morrow JD, Dey SK. Coordinated regulation of fetal and maternal prostaglandins directs successful birth and postnatal adaptation in the mouse. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9759-64. doi: 10.1073/pnas.97.17.9759.
Results Reference
background
PubMed Identifier
19390487
Citation
Reese J, Waleh N, Poole SD, Brown N, Roman C, Clyman RI. Chronic in utero cyclooxygenase inhibition alters PGE2-regulated ductus arteriosus contractile pathways and prevents postnatal closure. Pediatr Res. 2009 Aug;66(2):155-61. doi: 10.1203/PDR.0b013e3181aa07eb.
Results Reference
background
PubMed Identifier
16238543
Citation
Derzbach L, Treszl A, Balogh A, Vasarhelyi B, Tulassay T, Rigo J J. Gender dependent association between perinatal morbidity and estrogen receptor-alpha Pvull polymorphism. J Perinat Med. 2005;33(5):461-2. doi: 10.1515/JPM.2005.082.
Results Reference
background
PubMed Identifier
16754651
Citation
Bokodi G, Derzbach L, Banyasz I, Tulassay T, Vasarhelyi B. Association of interferon gamma T+874A and interleukin 12 p40 promoter CTCTAA/GC polymorphism with the need for respiratory support and perinatal complications in low birthweight neonates. Arch Dis Child Fetal Neonatal Ed. 2007 Jan;92(1):F25-9. doi: 10.1136/adc.2005.086421. Epub 2006 Jun 5.
Results Reference
background
PubMed Identifier
8618179
Citation
Gonzalez A, Sosenko IR, Chandar J, Hummler H, Claure N, Bancalari E. Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less. J Pediatr. 1996 Apr;128(4):470-8. doi: 10.1016/s0022-3476(96)70356-6.
Results Reference
background
PubMed Identifier
7699543
Citation
Rojas MA, Gonzalez A, Bancalari E, Claure N, Poole C, Silva-Neto G. Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease. J Pediatr. 1995 Apr;126(4):605-10. doi: 10.1016/s0022-3476(95)70362-4.
Results Reference
background
PubMed Identifier
20581741
Citation
Waleh N, Hodnick R, Jhaveri N, McConaghy S, Dagle J, Seidner S, McCurnin D, Murray JC, Ohls R, Clyman RI. Patterns of gene expression in the ductus arteriosus are related to environmental and genetic risk factors for persistent ductus patency. Pediatr Res. 2010 Oct;68(4):292-7. doi: 10.1203/PDR.0b013e3181ed8609.
Results Reference
background
PubMed Identifier
13320399
Citation
BORN GV, DAWES GS, MOTT JC, RENNICK BR. The constriction of the ductus arteriosus caused by oxygen and by asphyxia in newborn lambs. J Physiol. 1956 May 28;132(2):304-42. doi: 10.1113/jphysiol.1956.sp005526. No abstract available.
Results Reference
background
PubMed Identifier
14078057
Citation
KOVALCIK V. THE RESPONSE OF THE ISOLATED DUCTUS ARTERIOSUS TO OXYGEN AND ANOXIA. J Physiol. 1963 Nov;169(1):185-97. doi: 10.1113/jphysiol.1963.sp007249. No abstract available.
Results Reference
background
PubMed Identifier
14169640
Citation
MOSS AJ, EMMANOUILIDES GC, ADAMS FH, CHUANG K. RESPONSE OF DUCTUS ARTERIOSUS AND PULMONARY AND SYSTEMIC ARTERIAL PRESSURE TO CHANGES IN OXYGEN ENVIRONMENT IN NEWBORN INFANTS. Pediatrics. 1964 Jun;33:937-44. No abstract available.
Results Reference
background
PubMed Identifier
5560296
Citation
Fay FS. Guinea pig ductus arteriosus. I. Cellular and metabolic basis for oxygen sensitivity. Am J Physiol. 1971 Aug;221(2):470-9. doi: 10.1152/ajplegacy.1971.221.2.470. No abstract available.
Results Reference
background
PubMed Identifier
9549757
Citation
Smith GC. The pharmacology of the ductus arteriosus. Pharmacol Rev. 1998 Mar;50(1):35-58. No abstract available.
Results Reference
background
PubMed Identifier
18036551
Citation
Ward JP. Oxygen sensors in context. Biochim Biophys Acta. 2008 Jan;1777(1):1-14. doi: 10.1016/j.bbabio.2007.10.010. Epub 2007 Nov 1.
Results Reference
background
PubMed Identifier
18206805
Citation
Fleming I. Vascular cytochrome p450 enzymes: physiology and pathophysiology. Trends Cardiovasc Med. 2008 Jan;18(1):20-5. doi: 10.1016/j.tcm.2007.11.002.
Results Reference
background
PubMed Identifier
19801493
Citation
Baragatti B, Schwartzman ML, Angeloni D, Scebba F, Ciofini E, Sodini D, Ottaviano V, Nencioni S, Paolicchi A, Graves JP, Zeldin DC, Gotlinger K, Luin S, Coceani F. EDHF function in the ductus arteriosus: evidence against involvement of epoxyeicosatrienoic acids and 12S-hydroxyeicosatetraenoic acid. Am J Physiol Heart Circ Physiol. 2009 Dec;297(6):H2161-8. doi: 10.1152/ajpheart.00576.2009. Epub 2009 Oct 2.
Results Reference
background
PubMed Identifier
7273368
Citation
Roulet MJ, Coburn RF. Oxygen-induced contraction in the guinea pig neonatal ductus arteriosus. Circ Res. 1981 Oct;49(4):997-1002. doi: 10.1161/01.res.49.4.997.
Results Reference
background
PubMed Identifier
8495551
Citation
Nakanishi T, Gu H, Hagiwara N, Momma K. Mechanisms of oxygen-induced contraction of ductus arteriosus isolated from the fetal rabbit. Circ Res. 1993 Jun;72(6):1218-28. doi: 10.1161/01.res.72.6.1218.
Results Reference
background
PubMed Identifier
8903313
Citation
Tristani-Firouzi M, Reeve HL, Tolarova S, Weir EK, Archer SL. Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of a 4-aminopyridine-, voltage-sensitive potassium channel. J Clin Invest. 1996 Nov 1;98(9):1959-65. doi: 10.1172/JCI118999.
Results Reference
background
PubMed Identifier
16282179
Citation
Weir EK, Lopez-Barneo J, Buckler KJ, Archer SL. Acute oxygen-sensing mechanisms. N Engl J Med. 2005 Nov 10;353(19):2042-55. doi: 10.1056/NEJMra050002. No abstract available.
Results Reference
background
PubMed Identifier
10963252
Citation
Michelakis E, Rebeyka I, Bateson J, Olley P, Puttagunta L, Archer S. Voltage-gated potassium channels in human ductus arteriosus. Lancet. 2000 Jul 8;356(9224):134-7. doi: 10.1016/S0140-6736(00)02452-1.
Results Reference
background
PubMed Identifier
15134333
Citation
Archer SL, Wu XC, Thebaud B, Moudgil R, Hashimoto K, Michelakis ED. O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide. Biol Chem. 2004 Mar-Apr;385(3-4):205-16. doi: 10.1515/BC.2004.014.
Results Reference
background
PubMed Identifier
4239830
Citation
Arcilla RA, Thilenius OG, Ranniger K. Congestive heart failure from suspected ductal closure in utero. J Pediatr. 1969 Jul;75(1):74-8. doi: 10.1016/s0022-3476(69)80103-4.
Results Reference
background
PubMed Identifier
4437814
Citation
Zuckerman H, Reiss U, Rubinstein I. Inhibition of human premature labor by indomethacin. Obstet Gynecol. 1974 Dec;44(6):787-92. No abstract available.
Results Reference
background
PubMed Identifier
4705142
Citation
Coceani F, Olley PM. The response of the ductus arteriosus to prostaglandins. Can J Physiol Pharmacol. 1973 Mar;51(3):220-5. doi: 10.1139/y73-031. No abstract available.
Results Reference
background
PubMed Identifier
1135442
Citation
Coceani F, Olley PM, Bodach E. Lamb ductus arteriosus: effect of prostaglandin synthesis inhibitors on the muscle tone and the response to prostaglandin E2. Prostaglandins. 1975 Feb;9(2):299-308. doi: 10.1016/0090-6980(75)90034-9.
Results Reference
background
PubMed Identifier
4453621
Citation
Sharpe GL, Thalme B, Larsson KS. Studies on closure of the ductus arteriosus. XI. Ductal closure in utero by a prostaglandin synthetase inhibitor. Prostaglandins. 1974 Dec 10;8(5):363-8. doi: 10.1016/0090-6980(74)90110-5. No abstract available.
Results Reference
background
PubMed Identifier
4215100
Citation
Starling MB, Elliott RB. The effects of prostaglandins, prostaglandin inhibitors, and oxygen on the closure of the ductus arteriosus, pulmonary arteries and umbilical vessels in vitro. Prostaglandins. 1974 Nov 10;8(3):187-203. doi: 10.1016/0090-6980(74)90042-2. No abstract available.
Results Reference
background
PubMed Identifier
820994
Citation
Friedman WF, Hirschklau MJ, Printz MP, Pitlick PT, Kirkpatrick SE. Pharmacologic closure of patent ductus arteriosus in the premature infant. N Engl J Med. 1976 Sep 2;295(10):526-9. doi: 10.1056/NEJM197609022951003.
Results Reference
background
PubMed Identifier
950959
Citation
Heymann MA, Rudolph AM, Silverman NH. Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. N Engl J Med. 1976 Sep 2;295(10):530-3. doi: 10.1056/NEJM197609022951004.
Results Reference
background
PubMed Identifier
899912
Citation
Coceani F, Olley PM, Bishai I, Bodach E, Heaton J, Nashat M, White E. Prostaglandins and the control of muscle tone in the ductus arteriosus. Adv Exp Med Biol. 1977;78:135-42. doi: 10.1007/978-1-4615-9035-4_10.
Results Reference
background
PubMed Identifier
497895
Citation
Coceani F, White E, Bodach E, Olley PM. Age-dependent changes in the response of the lamb ductus arteriosus to oxygen and ibuprofen. Can J Physiol Pharmacol. 1979 Aug;57(8):825-31. doi: 10.1139/y79-126.
Results Reference
background
PubMed Identifier
17060397
Citation
Schneider DJ, Moore JW. Patent ductus arteriosus. Circulation. 2006 Oct 24;114(17):1873-82. doi: 10.1161/CIRCULATIONAHA.105.592063. No abstract available.
Results Reference
background
PubMed Identifier
9890604
Citation
Clyman RI, Chan CY, Mauray F, Chen YQ, Cox W, Seidner SR, Lord EM, Weiss H, Waleh N, Evans SM, Koch CJ. Permanent anatomic closure of the ductus arteriosus in newborn baboons: the roles of postnatal constriction, hypoxia, and gestation. Pediatr Res. 1999 Jan;45(1):19-29. doi: 10.1203/00006450-199901000-00005.
Results Reference
background
PubMed Identifier
15695541
Citation
Keck M, Resnik E, Linden B, Anderson F, Sukovich DJ, Herron J, Cornfield DN. Oxygen increases ductus arteriosus smooth muscle cytosolic calcium via release of calcium from inositol triphosphate-sensitive stores. Am J Physiol Lung Cell Mol Physiol. 2005 May;288(5):L917-23. doi: 10.1152/ajplung.00403.2004. Epub 2005 Feb 4.
Results Reference
background
PubMed Identifier
18641675
Citation
Weir EK, Obreztchikova M, Vargese A, Cabrera JA, Peterson DA, Hong Z. Mechanisms of oxygen sensing: a key to therapy of pulmonary hypertension and patent ductus arteriosus. Br J Pharmacol. 2008 Oct;155(3):300-7. doi: 10.1038/bjp.2008.291. Epub 2008 Jul 21.
Results Reference
background
PubMed Identifier
15353504
Citation
Thebaud B, Michelakis ED, Wu XC, Moudgil R, Kuzyk M, Dyck JR, Harry G, Hashimoto K, Haromy A, Rebeyka I, Archer SL. Oxygen-sensitive Kv channel gene transfer confers oxygen responsiveness to preterm rabbit and remodeled human ductus arteriosus: implications for infants with patent ductus arteriosus. Circulation. 2004 Sep 14;110(11):1372-9. doi: 10.1161/01.CIR.0000141292.28616.65. Epub 2004 Sep 7.
Results Reference
background
PubMed Identifier
18091358
Citation
Thebaud B, Wu XC, Kajimoto H, Bonnet S, Hashimoto K, Michelakis ED, Archer SL. Developmental absence of the O2 sensitivity of L-type calcium channels in preterm ductus arteriosus smooth muscle cells impairs O2 constriction contributing to patent ductus arteriosus. Pediatr Res. 2008 Feb;63(2):176-81. doi: 10.1203/PDR.0b013e31815ed059.
Results Reference
background
PubMed Identifier
17353442
Citation
Kajimoto H, Hashimoto K, Bonnet SN, Haromy A, Harry G, Moudgil R, Nakanishi T, Rebeyka I, Thebaud B, Michelakis ED, Archer SL. Oxygen activates the Rho/Rho-kinase pathway and induces RhoB and ROCK-1 expression in human and rabbit ductus arteriosus by increasing mitochondria-derived reactive oxygen species: a newly recognized mechanism for sustaining ductal constriction. Circulation. 2007 Apr 3;115(13):1777-88. doi: 10.1161/CIRCULATIONAHA.106.649566. Epub 2007 Mar 12.
Results Reference
background
PubMed Identifier
16982938
Citation
Hong Z, Hong F, Olschewski A, Cabrera JA, Varghese A, Nelson DP, Weir EK. Role of store-operated calcium channels and calcium sensitization in normoxic contraction of the ductus arteriosus. Circulation. 2006 Sep 26;114(13):1372-9. doi: 10.1161/CIRCULATIONAHA.106.641126. Epub 2006 Sep 18.
Results Reference
background
PubMed Identifier
2054736
Citation
Coceani F, Kelsey L. Endothelin-1 release from lamb ductus arteriosus: relevance to postnatal closure of the vessel. Can J Physiol Pharmacol. 1991 Feb;69(2):218-21. doi: 10.1139/y91-033.
Results Reference
background
PubMed Identifier
9815069
Citation
Fineman JR, Takahashi Y, Roman C, Clyman RI. Endothelin-receptor blockade does not alter closure of the ductus arteriosus. Am J Physiol. 1998 Nov;275(5):H1620-6. doi: 10.1152/ajpheart.1998.275.5.H1620.
Results Reference
background
PubMed Identifier
7658282
Citation
Weiss H, Cooper B, Brook M, Schlueter M, Clyman R. Factors determining reopening of the ductus arteriosus after successful clinical closure with indomethacin. J Pediatr. 1995 Sep;127(3):466-71. doi: 10.1016/s0022-3476(95)70084-6.
Results Reference
background
PubMed Identifier
21217670
Citation
Fujioka K, Morioka I, Miwa A, Morikawa S, Shibata A, Yokoyama N, Matsuo M. Does thrombocytopenia contribute to patent ductus arteriosus? Nat Med. 2011 Jan;17(1):29-30; author reply 30-1. doi: 10.1038/nm0111-29. No abstract available.
Results Reference
background
PubMed Identifier
21195414
Citation
Shah NA, Hills NK, Waleh N, McCurnin D, Seidner S, Chemtob S, Clyman R. Relationship between circulating platelet counts and ductus arteriosus patency after indomethacin treatment. J Pediatr. 2011 Jun;158(6):919-923.e1-2. doi: 10.1016/j.jpeds.2010.11.018. Epub 2010 Dec 30.
Results Reference
background
PubMed Identifier
22717423
Citation
Alyamac Dizdar E, Ozdemir R, Sari FN, Yurttutan S, Gokmen T, Erdeve O, Emre Canpolat F, Uras N, Suna Oguz S, Dilmen U. Low platelet count is associated with ductus arteriosus patency in preterm newborns. Early Hum Dev. 2012 Oct;88(10):813-6. doi: 10.1016/j.earlhumdev.2012.05.007. Epub 2012 Jun 18.
Results Reference
background
PubMed Identifier
22869835
Citation
Sallmon H, Weber SC, Huning B, Stein A, Horn PA, Metze BC, Dame C, Buhrer C, Felderhoff-Muser U, Hansmann G, Koehne P. Thrombocytopenia in the first 24 hours after birth and incidence of patent ductus arteriosus. Pediatrics. 2012 Sep;130(3):e623-30. doi: 10.1542/peds.2012-0499. Epub 2012 Aug 6.
Results Reference
background
PubMed Identifier
25012267
Citation
Bas-Suarez MP, Gonzalez-Luis GE, Saavedra P, Villamor E. Platelet counts in the first seven days of life and patent ductus arteriosus in preterm very low-birth-weight infants. Neonatology. 2014;106(3):188-94. doi: 10.1159/000362432. Epub 2014 Jul 5.
Results Reference
background
PubMed Identifier
18582931
Citation
Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, Gawande AA. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet. 2008 Jul 12;372(9633):139-144. doi: 10.1016/S0140-6736(08)60878-8. Epub 2008 Jun 24.
Results Reference
background
PubMed Identifier
23633310
Citation
Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2013 Apr 30;(4):CD003481. doi: 10.1002/14651858.CD003481.pub5.
Results Reference
background
PubMed Identifier
17668683
Citation
O'Riordan JM, Fitzgerald J, Smith OP, Bonnar J, Gorman WA; National Blood Users Group. Transfusion of blood components to infants under four months: review and guidelines. Ir Med J. 2007 Jun;100(6):suppl 1-24 following 496. No abstract available.
Results Reference
background
PubMed Identifier
30940676
Citation
Kumar J, Dutta S, Sundaram V, Saini SS, Sharma RR, Varma N. Platelet Transfusion for PDA Closure in Preterm Infants: A Randomized Controlled Trial. Pediatrics. 2019 May;143(5):e20182565. doi: 10.1542/peds.2018-2565. Epub 2019 Apr 2.
Results Reference
derived
Links:
URL
http://www.transfusionguidelines.org.uk.
Description
Transfusion guidelines for surgical procedures.

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Platelet Transfusion for Treatment of Patent Ductus Arteriosus in Thrombocytopenic Preterm Neonates

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