search
Back to results

Outpatient Antibiotics Following Previable Rupture of Membranes (pPPROM) Between 18 0/7 and 22 6/7 Weeks Gestational Age

Primary Purpose

Pregnancy Preterm, Pregnancy Prom, PROM, Preterm (Pregnancy)

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Azithromycin Pill
Amoxicillin Pill
Sponsored by
University Hospitals Cleveland Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pregnancy Preterm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • English-speaking
  • Pregnant
  • Live, singleton gestation
  • Patient able to provide informed consent
  • Gestational age between 18 weeks and 0 days and 22 weeks and 6 days at the time of -membrane rupture
  • Diagnosis of preterm, prelabor rupture of membranes by clinical exam findings of either 1) visualization of amniotic fluid passing from the cervical canal and/or pooling in the vagina via sterile speculum examination, 2) a basic pH (i.e., positive nitrazine) test of vaginal fluid, 3) arborization (i.e., ferning) of dried vaginal fluid identified via microscopic examination, and/or 4) an amniotic fluid index (AFI) of less than 4cm

Exclusion Criteria:

  • Gestational dating performed or confirmed by ultrasound at ≥ 18 weeks and 0 days gestational age
  • Patient desires pregnancy interruption or induction of labor
  • Known major fetal anomaly or aneuploidy
  • Amniocentesis ≤ 7 days of diagnosis of rupture of membranes
  • Cervical cerclage placement ≤ 7 days of diagnosis of rupture of membranes
  • Known drug allergy or significant adverse reactions to macrolide or penicillin antibiotics
  • Current antibiotic use at the time of membrane rupture diagnosis
  • Vaginal bleeding at the time of membrane rupture diagnosis or within first 24 hours from diagnosis
  • Febrile at the time of membrane rupture diagnosis (i.e., temperature ≥ 38 degrees Celsius) and/or within first 24 hours of diagnosis
  • Active preterm labor at the time of membrane rupture diagnosis (i.e., consistent contraction pattern associated with cervical change) and/or within first 24 hours of diagnosis
  • Cervical dilation of ≥ 4 cm
  • Prolapse of fetal parts beyond the level of the internal cervical os
  • Declination to complete full, 7-day outpatient monitoring prior to hospital re-admission should rupture occur during the 22nd week of gestation

Sites / Locations

  • University Hospitals
  • MetroHealthRecruiting
  • Cleveland Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Antibiotics

No antibiotics

Arm Description

Patients randomized into the treatment (i.e., antibiotics) arm of the study will be treated with a seven-day course of oral azithromycin and amoxicillin. Azithromycin will be dosed as single 500 mg dose (2-250mg oral tablets) administered immediately following randomization, yet prior to discharge to home, followed with 1-250mg oral tablet daily for 4 additional days (for a total of 5 days). Amoxicillin will be dosed as a single-500mg oral tablet three times daily for 7 days with first dose also being given prior to discharge home.

Patients randomized into the control (i.e., no antibiotics arm) will be managed according to standard of care practices for previable PPROM desiring of expectant management.

Outcomes

Primary Outcome Measures

Delivery within 28 days
The proportion of patients that undergo a spontaneous or medically-indicated delivery within 28 days from diagnosis of previable prelabor rupture of membranes (pPPROM)

Secondary Outcome Measures

Severe maternal morbidity composite
The proportion of patient's "positive" for severe maternal morbidity composite. A patient will be termed "positive" for severe maternal morbidity composite if any one of the following is diagnosed: maternal sepsis, postpartum hemorrhage, maternal ICU admission, maternal death.
Severe neonatal morbidity composite
The proportion of patient's "positive" for severe neonatal morbidity composite. A neonate will be termed "positive" for severe neonatal morbidity composite if any one of the following is diagnosis: bronchopulmonary dysplasia (BPD), pulmonary hypoplasia, intraventricular hemorrhage (IVH) grade III/IV, necrotizing enterocolitis (NEC) Bell's Stage II or greater, neonatal sepsis with positive blood cultures, neonatal pneumonia with positive blood cultures, neonatal death.

Full Information

First Posted
April 14, 2022
Last Updated
February 11, 2023
Sponsor
University Hospitals Cleveland Medical Center
Collaborators
MetroHealth Medical Center, The Cleveland Clinic
search

1. Study Identification

Unique Protocol Identification Number
NCT05345457
Brief Title
Outpatient Antibiotics Following Previable Rupture of Membranes (pPPROM) Between 18 0/7 and 22 6/7 Weeks Gestational Age
Official Title
Outpatient Antibiotics Following Previable Rupture of Membranes (pPPROM) Between 18 0/7 and 22 6/7 Weeks Gestational Age
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 13, 2023 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospitals Cleveland Medical Center
Collaborators
MetroHealth Medical Center, The Cleveland Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A randomized, controlled, non-placebo trial to primarily assess the effect of oral, outpatient antibiotics (i.e., azithromycin and amoxicillin) on latency (i.e., proportion of patients that deliver within 28 days from membrane rupture) following previable, prelabor rupture of membranes between 18 0/7 and 22 6/7 weeks gestational age.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pregnancy Preterm, Pregnancy Prom, PROM, Preterm (Pregnancy), PROM (Pregnancy), Premat Rupture Membranes Preterm Unspec to Length of Time Between Rupture/Labor, Premature Birth

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
88 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Antibiotics
Arm Type
Experimental
Arm Description
Patients randomized into the treatment (i.e., antibiotics) arm of the study will be treated with a seven-day course of oral azithromycin and amoxicillin. Azithromycin will be dosed as single 500 mg dose (2-250mg oral tablets) administered immediately following randomization, yet prior to discharge to home, followed with 1-250mg oral tablet daily for 4 additional days (for a total of 5 days). Amoxicillin will be dosed as a single-500mg oral tablet three times daily for 7 days with first dose also being given prior to discharge home.
Arm Title
No antibiotics
Arm Type
No Intervention
Arm Description
Patients randomized into the control (i.e., no antibiotics arm) will be managed according to standard of care practices for previable PPROM desiring of expectant management.
Intervention Type
Drug
Intervention Name(s)
Azithromycin Pill
Intervention Description
Azithromycin will be dosed as single 500 mg dose (2-250mg oral tablets) administered immediately following randomization, yet prior to discharge to home, followed with 1-250mg oral tablet daily for 4 additional days (for a total of 5 days).
Intervention Type
Drug
Intervention Name(s)
Amoxicillin Pill
Intervention Description
Amoxicillin will be dosed as a single-500mg oral tablet three times daily for 7 days with first dose also being given prior to discharge home.
Primary Outcome Measure Information:
Title
Delivery within 28 days
Description
The proportion of patients that undergo a spontaneous or medically-indicated delivery within 28 days from diagnosis of previable prelabor rupture of membranes (pPPROM)
Time Frame
28 days from date of rupture
Secondary Outcome Measure Information:
Title
Severe maternal morbidity composite
Description
The proportion of patient's "positive" for severe maternal morbidity composite. A patient will be termed "positive" for severe maternal morbidity composite if any one of the following is diagnosed: maternal sepsis, postpartum hemorrhage, maternal ICU admission, maternal death.
Time Frame
From diagnosis of membrane rupture to 6 weeks following delivery
Title
Severe neonatal morbidity composite
Description
The proportion of patient's "positive" for severe neonatal morbidity composite. A neonate will be termed "positive" for severe neonatal morbidity composite if any one of the following is diagnosis: bronchopulmonary dysplasia (BPD), pulmonary hypoplasia, intraventricular hemorrhage (IVH) grade III/IV, necrotizing enterocolitis (NEC) Bell's Stage II or greater, neonatal sepsis with positive blood cultures, neonatal pneumonia with positive blood cultures, neonatal death.
Time Frame
From date of delivery to date of hospital discharge (up to 6 months)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: English-speaking Pregnant Live, singleton gestation Patient able to provide informed consent Gestational age between 18 weeks and 0 days and 22 weeks and 6 days at the time of -membrane rupture Diagnosis of preterm, prelabor rupture of membranes by clinical exam findings of either 1) visualization of amniotic fluid passing from the cervical canal and/or pooling in the vagina via sterile speculum examination, 2) a basic pH (i.e., positive nitrazine) test of vaginal fluid, 3) arborization (i.e., ferning) of dried vaginal fluid identified via microscopic examination, and/or 4) an amniotic fluid index (AFI) of less than 4cm Exclusion Criteria: Gestational dating performed or confirmed by ultrasound at ≥ 18 weeks and 0 days gestational age Patient desires pregnancy interruption or induction of labor Known major fetal anomaly or aneuploidy Amniocentesis ≤ 7 days of diagnosis of rupture of membranes Cervical cerclage placement ≤ 7 days of diagnosis of rupture of membranes Known drug allergy or significant adverse reactions to macrolide or penicillin antibiotics Current antibiotic use at the time of membrane rupture diagnosis Vaginal bleeding at the time of membrane rupture diagnosis or within first 24 hours from diagnosis Febrile at the time of membrane rupture diagnosis (i.e., temperature ≥ 38 degrees Celsius) and/or within first 24 hours of diagnosis Active preterm labor at the time of membrane rupture diagnosis (i.e., consistent contraction pattern associated with cervical change) and/or within first 24 hours of diagnosis Cervical dilation of ≥ 4 cm Prolapse of fetal parts beyond the level of the internal cervical os Declination to complete full, 7-day outpatient monitoring prior to hospital re-admission should rupture occur during the 22nd week of gestation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Felicia LeMoine, MD
Phone
(216) 983-6606
Email
felicia.lemoine@uhhospitals.org
First Name & Middle Initial & Last Name or Official Title & Degree
David Hackney, MD
Phone
(216) 844-3787
Email
david.hackney@uhhospitals.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Hackney, MD
Organizational Affiliation
University Hospitals Cleveland Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Justin Lappen, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Brian Mercer, MD
Organizational Affiliation
MetroHealth Hospitals
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Felicia LeMoine, MD
Phone
216-983-6606
Email
felicia.lemoine@uhhosptials.org
Facility Name
MetroHealth
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Felicia LeMoine, MD
Phone
216-983-6606
Email
felicia.lemoine@uhhospitals.org
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44111
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Felicia LeMoine, MD
Phone
216-983-6606
Email
felicia.lemoine@uhhospitals.org

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Once data collection and primary analysis has been completed. A de-identified data set will be provided.
IPD Sharing Time Frame
Data will become available upon publication of study results and remain available for 2 years upon study completion.
Citations:
PubMed Identifier
24974589
Citation
Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Wilson EC, Mathews TJ. Births: final data for 2010. Natl Vital Stat Rep. 2012 Aug 28;61(1):1-72.
Results Reference
background
PubMed Identifier
20815136
Citation
Mathews TJ, MacDorman MF. Infant mortality statistics from the 2006 period linked birth/infant death data set. Natl Vital Stat Rep. 2010 Apr 30;58(17):1-31.
Results Reference
background
PubMed Identifier
21508700
Citation
Waters TP, Mercer B. Preterm PROM: prediction, prevention, principles. Clin Obstet Gynecol. 2011 Jun;54(2):307-12. doi: 10.1097/GRF.0b013e318217d4d3.
Results Reference
background
PubMed Identifier
11817188
Citation
Kilbride HW, Thibeault DW. Neonatal complications of preterm premature rupture of membranes. Pathophysiology and management. Clin Perinatol. 2001 Dec;28(4):761-85. doi: 10.1016/s0095-5108(03)00076-9.
Results Reference
background
PubMed Identifier
11758532
Citation
Yeast JD. Preterm premature rupture of the membranes before viability. Clin Perinatol. 2001 Dec;28(4):849-60. doi: 10.1016/s0095-5108(03)00082-4.
Results Reference
background
PubMed Identifier
16846673
Citation
Muris C, Girard B, Creveuil C, Durin L, Herlicoviez M, Dreyfus M. Management of premature rupture of membranes before 25 weeks. Eur J Obstet Gynecol Reprod Biol. 2007 Apr;131(2):163-8. doi: 10.1016/j.ejogrb.2006.05.016. Epub 2006 Jul 17.
Results Reference
background
PubMed Identifier
9307346
Citation
Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL, Das AF, Ramsey RD, Rabello YA, Meis PJ, Moawad AH, Iams JD, Van Dorsten JP, Paul RH, Bottoms SF, Merenstein G, Thom EA, Roberts JM, McNellis D. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. JAMA. 1997 Sep 24;278(12):989-95.
Results Reference
background
PubMed Identifier
28937572
Citation
American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine. Obstetric Care consensus No. 6: Periviable Birth. Obstet Gynecol. 2017 Oct;130(4):e187-e199. doi: 10.1097/AOG.0000000000002352.
Results Reference
background
PubMed Identifier
12732862
Citation
Grisaru-Granovsky S, Eitan R, Kaplan M, Samueloff A. Expectant management of midtrimester premature rupture of membranes: a plea for limits. J Perinatol. 2003 Apr-May;23(3):235-9. doi: 10.1038/sj.jp.7210880.
Results Reference
background
PubMed Identifier
8912993
Citation
Schucker JL, Mercer BM. Midtrimester premature rupture of the membranes. Semin Perinatol. 1996 Oct;20(5):389-400. doi: 10.1016/s0146-0005(96)80006-1.
Results Reference
background
PubMed Identifier
19733274
Citation
Waters TP, Mercer BM. The management of preterm premature rupture of the membranes near the limit of fetal viability. Am J Obstet Gynecol. 2009 Sep;201(3):230-40. doi: 10.1016/j.ajog.2009.06.049.
Results Reference
background
PubMed Identifier
18289539
Citation
Pristauz G, Bauer M, Maurer-Fellbaum U, Rotky-Fast C, Bader AA, Haas J, Lang U. Neonatal outcome and two-year follow-up after expectant management of second trimester rupture of membranes. Int J Gynaecol Obstet. 2008 Jun;101(3):264-8. doi: 10.1016/j.ijgo.2007.12.007. Epub 2008 Mar 4.
Results Reference
background
PubMed Identifier
29286934
Citation
Dotters-Katz SK, Myrick O, Smid M, Manuck TA, Boggess KA, Goodnight W. Use of prophylactic antibiotics in women with previable prelabor rupture of membranes. J Neonatal Perinatal Med. 2017;10(4):431-437. doi: 10.3233/NPM-16165.
Results Reference
background
PubMed Identifier
19546755
Citation
Manuck TA, Eller AG, Esplin MS, Stoddard GJ, Varner MW, Silver RM. Outcomes of expectantly managed preterm premature rupture of membranes occurring before 24 weeks of gestation. Obstet Gynecol. 2009 Jul;114(1):29-37. doi: 10.1097/AOG.0b013e3181ab6fd3.
Results Reference
background
PubMed Identifier
26138545
Citation
Esteves JS, de Sa RA, de Carvalho PR, Coca Velarde LG. Neonatal outcome in women with preterm premature rupture of membranes (PPROM) between 18 and 26 weeks. J Matern Fetal Neonatal Med. 2016;29(7):1108-12. doi: 10.3109/14767058.2015.1035643. Epub 2015 Jul 3.
Results Reference
background
PubMed Identifier
26831896
Citation
Linehan LA, Walsh J, Morris A, Kenny L, O'Donoghue K, Dempsey E, Russell N. Neonatal and maternal outcomes following midtrimester preterm premature rupture of the membranes: a retrospective cohort study. BMC Pregnancy Childbirth. 2016 Jan 29;16:25. doi: 10.1186/s12884-016-0813-3.
Results Reference
background
PubMed Identifier
20233131
Citation
Deutsch A, Deutsch E, Totten C, Downes K, Haubner L, Belogolovkin V. Maternal and neonatal outcomes based on the gestational age of midtrimester preterm premature rupture of membranes. J Matern Fetal Neonatal Med. 2010 Dec;23(12):1429-34. doi: 10.3109/14767051003678069. Epub 2010 Mar 17.
Results Reference
background
PubMed Identifier
23212880
Citation
Moore T, Hennessy EM, Myles J, Johnson SJ, Draper ES, Costeloe KL, Marlow N. Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies. BMJ. 2012 Dec 4;345:e7961. doi: 10.1136/bmj.e7961.
Results Reference
background
PubMed Identifier
24297389
Citation
Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev. 2013 Dec 2;(12):CD001058. doi: 10.1002/14651858.CD001058.pub3.
Results Reference
background
PubMed Identifier
7475723
Citation
Mercer BM, Arheart KL. Antimicrobial therapy in expectant management of preterm premature rupture of the membranes. Lancet. 1995 Nov 11;346(8985):1271-9. doi: 10.1016/s0140-6736(95)91868-x. Erratum In: Lancet 1996 Feb 10;347(8998):410.
Results Reference
background
PubMed Identifier
11293640
Citation
Kenyon SL, Taylor DJ, Tarnow-Mordi W; ORACLE Collaborative Group. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group. Lancet. 2001 Mar 31;357(9261):979-88. doi: 10.1016/s0140-6736(00)04233-1. Erratum In: Lancet 2001 Jul 14;358(9276):156.
Results Reference
background
PubMed Identifier
1550145
Citation
Mercer BM, Moretti ML, Prevost RR, Sibai BM. Erythromycin therapy in preterm premature rupture of the membranes: a prospective, randomized trial of 220 patients. Am J Obstet Gynecol. 1992 Mar;166(3):794-802. doi: 10.1016/0002-9378(92)91336-9.
Results Reference
background
PubMed Identifier
20335313
Citation
Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med. 2010 Jun 1;152(11):726-32. doi: 10.7326/0003-4819-152-11-201006010-00232. Epub 2010 Mar 24.
Results Reference
background
PubMed Identifier
30904320
Citation
Navathe R, Schoen CN, Heidari P, Bachilova S, Ward A, Tepper J, Visintainer P, Hoffman MK, Smith S, Berghella V, Roman A. Azithromycin vs erythromycin for the management of preterm premature rupture of membranes. Am J Obstet Gynecol. 2019 Aug;221(2):144.e1-144.e8. doi: 10.1016/j.ajog.2019.03.009. Epub 2019 Mar 20.
Results Reference
background
PubMed Identifier
19160238
Citation
Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD004661. doi: 10.1002/14651858.CD004661.pub3.
Results Reference
background
PubMed Identifier
20331587
Citation
DiGiulio DB, Romero R, Kusanovic JP, Gomez R, Kim CJ, Seok KS, Gotsch F, Mazaki-Tovi S, Vaisbuch E, Sanders K, Bik EM, Chaiworapongsa T, Oyarzun E, Relman DA. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol. 2010 Jul 1;64(1):38-57. doi: 10.1111/j.1600-0897.2010.00830.x. Epub 2010 Mar 21.
Results Reference
background
PubMed Identifier
2410839
Citation
Broekhuizen FF, Gilman M, Hamilton PR. Amniocentesis for gram stain and culture in preterm premature rupture of the membranes. Obstet Gynecol. 1985 Sep;66(3):316-21.
Results Reference
background
PubMed Identifier
6691016
Citation
Cotton DB, Hill LM, Strassner HT, Platt LD, Ledger WJ. Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol. 1984 Jan;63(1):38-43.
Results Reference
background
PubMed Identifier
6492031
Citation
Zlatnik FJ, Cruikshank DP, Petzold CR, Galask RP. Amniocentesis in the identification of inapparent infection in preterm patients with premature rupture of the membranes. J Reprod Med. 1984 Sep;29(9):656-60.
Results Reference
background
PubMed Identifier
20678747
Citation
Oh KJ, Lee KA, Sohn YK, Park CW, Hong JS, Romero R, Yoon BH. Intraamniotic infection with genital mycoplasmas exhibits a more intense inflammatory response than intraamniotic infection with other microorganisms in patients with preterm premature rupture of membranes. Am J Obstet Gynecol. 2010 Sep;203(3):211.e1-8. doi: 10.1016/j.ajog.2010.03.035. Epub 2010 Aug 3.
Results Reference
background
PubMed Identifier
2456013
Citation
Romero R, Emamian M, Quintero R, Wan M, Hobbins JC, Mazor M, Edberg S. The value and limitations of the Gram stain examination in the diagnosis of intraamniotic infection. Am J Obstet Gynecol. 1988 Jul;159(1):114-9. doi: 10.1016/0002-9378(88)90503-0.
Results Reference
background
PubMed Identifier
10847234
Citation
Heikkinen T, Laine K, Neuvonen PJ, Ekblad U. The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin. BJOG. 2000 Jun;107(6):770-5. doi: 10.1111/j.1471-0528.2000.tb13339.x.
Results Reference
background
PubMed Identifier
8851453
Citation
Amsden GW. Erythromycin, clarithromycin, and azithromycin: are the differences real? Clin Ther. 1996 Jan-Feb;18(1):56-72; discussion 55. doi: 10.1016/s0149-2918(96)80179-2.
Results Reference
background
PubMed Identifier
25111234
Citation
Martinez MA, Vuppalanchi R, Fontana RJ, Stolz A, Kleiner DE, Hayashi PH, Gu J, Hoofnagle JH, Chalasani N. Clinical and histologic features of azithromycin-induced liver injury. Clin Gastroenterol Hepatol. 2015 Feb;13(2):369-376.e3. doi: 10.1016/j.cgh.2014.07.054. Epub 2014 Aug 9.
Results Reference
background
PubMed Identifier
16856707
Citation
Russo V, Puzio G, Siniscalchi N. Azithromycin-induced QT prolongation in elderly patient. Acta Biomed. 2006 Apr;77(1):30-2.
Results Reference
background
PubMed Identifier
17546486
Citation
Kezerashvili A, Khattak H, Barsky A, Nazari R, Fisher JD. Azithromycin as a cause of QT-interval prolongation and torsade de pointes in the absence of other known precipitating factors. J Interv Card Electrophysiol. 2007 Apr;18(3):243-6. doi: 10.1007/s10840-007-9124-y. Epub 2007 Jun 2.
Results Reference
background
PubMed Identifier
27891788
Citation
Ailes EC, Gilboa SM, Gill SK, Broussard CS, Crider KS, Berry RJ, Carter TC, Hobbs CA, Interrante JD, Reefhuis J; and The National Birth Defects Prevention Study. Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011. Birth Defects Res A Clin Mol Teratol. 2016 Nov;106(11):940-949. doi: 10.1002/bdra.23570.
Results Reference
background
PubMed Identifier
9736566
Citation
Andes D, Craig WA. In vivo activities of amoxicillin and amoxicillin-clavulanate against Streptococcus pneumoniae: application to breakpoint determinations. Antimicrob Agents Chemother. 1998 Sep;42(9):2375-9. doi: 10.1128/AAC.42.9.2375.
Results Reference
background
PubMed Identifier
17329990
Citation
Andrew MA, Easterling TR, Carr DB, Shen D, Buchanan ML, Rutherford T, Bennett R, Vicini P, Hebert MF. Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies. Clin Pharmacol Ther. 2007 Apr;81(4):547-56. doi: 10.1038/sj.clpt.6100126. Epub 2007 Feb 28.
Results Reference
background
PubMed Identifier
26598097
Citation
Bookstaver PB, Bland CM, Griffin B, Stover KR, Eiland LS, McLaughlin M. A Review of Antibiotic Use in Pregnancy. Pharmacotherapy. 2015 Nov;35(11):1052-62. doi: 10.1002/phar.1649.
Results Reference
background
PubMed Identifier
19884587
Citation
Crider KS, Cleves MA, Reefhuis J, Berry RJ, Hobbs CA, Hu DJ. Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study. Arch Pediatr Adolesc Med. 2009 Nov;163(11):978-85. doi: 10.1001/archpediatrics.2009.188.
Results Reference
background
PubMed Identifier
11408852
Citation
Jacobson GF, Autry AM, Kirby RS, Liverman EM, Motley RU. A randomized controlled trial comparing amoxicillin and azithromycin for the treatment of Chlamydia trachomatis in pregnancy. Am J Obstet Gynecol. 2001 Jun;184(7):1352-4; discussion 1354-6. doi: 10.1067/mob.2001.115050.
Results Reference
background
PubMed Identifier
25189188
Citation
Lamont HF, Blogg HJ, Lamont RF. Safety of antimicrobial treatment during pregnancy: a current review of resistance, immunomodulation and teratogenicity. Expert Opin Drug Saf. 2014 Dec;13(12):1569-81. doi: 10.1517/14740338.2014.939580. Epub 2014 Sep 5.
Results Reference
background
PubMed Identifier
28722171
Citation
Muanda FT, Sheehy O, Berard A. Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study. Br J Clin Pharmacol. 2017 Nov;83(11):2557-2571. doi: 10.1111/bcp.13364. Epub 2017 Aug 11.
Results Reference
background
PubMed Identifier
19164154
Citation
Muller AE, Oostvogel PM, DeJongh J, Mouton JW, Steegers EA, Dorr PJ, Danhof M, Voskuyl RA. Pharmacokinetics of amoxicillin in maternal, umbilical cord, and neonatal sera. Antimicrob Agents Chemother. 2009 Apr;53(4):1574-80. doi: 10.1128/AAC.00119-08. Epub 2009 Jan 21.
Results Reference
background
PubMed Identifier
34271183
Citation
Piotin A, Godet J, Trubiano JA, Grandbastien M, Guenard-Bilbault L, de Blay F, Metz-Favre C. Predictive factors of amoxicillin immediate hypersensitivity and validation of PEN-FAST clinical decision rule. Ann Allergy Asthma Immunol. 2022 Jan;128(1):27-32. doi: 10.1016/j.anai.2021.07.005. Epub 2021 Jul 13. Erratum In: Ann Allergy Asthma Immunol. 2022 Jun;128(6):740.
Results Reference
background
PubMed Identifier
34306301
Citation
Koosakulchai V, Sangsupawanich P, Wantanaset D, Jessadapakorn W, Jongvilaikasem P, Yuenyongviwat A. Safety of direct oral provocation testing using the Amoxicillin-2-step-challenge in children with history of non-immediate reactions to amoxicillin. World Allergy Organ J. 2021 Jul 9;14(7):100560. doi: 10.1016/j.waojou.2021.100560. eCollection 2021 Jul.
Results Reference
background
PubMed Identifier
33292467
Citation
Schrufer P, Brockow K, Stoevesandt J, Trautmann A. Predominant patterns of beta-lactam hypersensitivity in a single German Allergy Center: exanthem induced by aminopenicillins, anaphylaxis by cephalosporins. Allergy Asthma Clin Immunol. 2020 Nov 17;16(1):102. doi: 10.1186/s13223-020-00488-0.
Results Reference
background
PubMed Identifier
30051945
Citation
Rodriguez-Martin S, Martin-Merino E, Lerma V, Rodriguez-Miguel A, Gonzalez O, Gonzalez-Herrada C, Ramirez E, Bellon T, de Abajo FJ. Active surveillance of severe cutaneous adverse reactions: A case-population approach using a registry and a health care database. Pharmacoepidemiol Drug Saf. 2018 Sep;27(9):1042-1050. doi: 10.1002/pds.4622. Epub 2018 Jul 27.
Results Reference
background
PubMed Identifier
31614216
Citation
Yang MS, Lee JY, Kim J, Kim GW, Kim BK, Kim JY, Park HW, Cho SH, Min KU, Kang HR. Searching for the Culprit Drugs for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis from a Nationwide Claim Database in Korea. J Allergy Clin Immunol Pract. 2020 Feb;8(2):690-695.e2. doi: 10.1016/j.jaip.2019.09.032. Epub 2019 Oct 12.
Results Reference
background
PubMed Identifier
25964726
Citation
Kuehn J, Ismael Z, Long PF, Barker CI, Sharland M. Reported rates of diarrhea following oral penicillin therapy in pediatric clinical trials. J Pediatr Pharmacol Ther. 2015 Mar-Apr;20(2):90-104. doi: 10.5863/1551-6776-20.2.90.
Results Reference
background
PubMed Identifier
27003987
Citation
McFarland LV, Ozen M, Dinleyici EC, Goh S. Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections. World J Gastroenterol. 2016 Mar 21;22(11):3078-104. doi: 10.3748/wjg.v22.i11.3078.
Results Reference
background
PubMed Identifier
29408016
Citation
Nasiri MJ, Goudarzi M, Hajikhani B, Ghazi M, Goudarzi H, Pouriran R. Clostridioides (Clostridium) difficile infection in hospitalized patients with antibiotic-associated diarrhea: A systematic review and meta-analysis. Anaerobe. 2018 Apr;50:32-37. doi: 10.1016/j.anaerobe.2018.01.011. Epub 2018 Jan 31.
Results Reference
background
PubMed Identifier
17385141
Citation
Peled N, Pitlik S, Samra Z, Kazakov A, Bloch Y, Bishara J. Predicting Clostridium difficile toxin in hospitalized patients with antibiotic-associated diarrhea. Infect Control Hosp Epidemiol. 2007 Apr;28(4):377-81. doi: 10.1086/513723. Epub 2007 Mar 9.
Results Reference
background
PubMed Identifier
6702914
Citation
Nimrod C, Varela-Gittings F, Machin G, Campbell D, Wesenberg R. The effect of very prolonged membrane rupture on fetal development. Am J Obstet Gynecol. 1984 Mar 1;148(5):540-3. doi: 10.1016/0002-9378(84)90743-9.
Results Reference
background
PubMed Identifier
10508984
Citation
Christianson C, Huff D, McPherson E. Limb deformations in oligohydramnios sequence: effects of gestational age and duration of oligohydramnios. Am J Med Genet. 1999 Oct 29;86(5):430-3.
Results Reference
background
PubMed Identifier
10871491
Citation
Winn HN, Chen M, Amon E, Leet TL, Shumway JB, Mostello D. Neonatal pulmonary hypoplasia and perinatal mortality in patients with midtrimester rupture of amniotic membranes--a critical analysis. Am J Obstet Gynecol. 2000 Jun;182(6):1638-44. doi: 10.1067/mob.2000.107435.
Results Reference
background

Learn more about this trial

Outpatient Antibiotics Following Previable Rupture of Membranes (pPPROM) Between 18 0/7 and 22 6/7 Weeks Gestational Age

We'll reach out to this number within 24 hrs