Postpartum NSAIDS and Maternal Hypertension
Primary Purpose
Preeclampsia, Gestational Hypertension, Superimposed Preeclampsia
Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ibuprofen 600 mg
Standard Postpartum Care without NSAIDs
Sponsored by
About this trial
This is an interventional treatment trial for Preeclampsia
Eligibility Criteria
Inclusion Criteria:
- Women 18 years or older delivering at LAC/USC Hospital
- Delivery occurring at or after 20 weeks gestation
- Diagnosis of antenatal hypertensive disorder: gestational hypertension, preeclampsia without severe features, preeclampsia with severe features, superimposed preeclampsia, eclampsia, chronic hypertension
Exclusion Criteria:
- HELLP Syndrome
- Renal dysfunction (Serum Creatinine >1.1 in current pregnancy)
- Known liver disease
- Low platelet count (<50,000 during hospital admission)
- Known sensitivity or allergy to ibuprofen or acetaminophen
- Use of therapeutic doses of anticoagulation
- Postpartum hemorrhage requiring blood transfusion
- Neonate with platelet disorder or thrombocytopenia in breastfeeding mother
Sites / Locations
- LA County Hospital/University of Southern CaliforniaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Standard Postpartum Care
Standard Postpartum Care without NSAIDs
Arm Description
Subjects will receive NSAIDs (e.g. ibuprofen, ketorolac) for routine postpartum pain management.
Subjects will receive standard postpartum care without NSAID administration for pain management. Acetaminophen or narcotics will be substituted for ibuprofen as indicated by provider.
Outcomes
Primary Outcome Measures
Proportion of participants with blood pressure elevation
Incidence of Systolic Blood Pressure of 150 mmHg or Diastolic Blood Pressure of 100 mmHg or above
Secondary Outcome Measures
Proportion of participants with blood pressure elevation
Incidence of Systolic Blood Pressure of 150 mmHg or Diastolic Blood Pressure of 100 mmHg or above
Number of participants with eclamptic Seizure
Documented occurrence of new onset generalized tonic-clonic seizure(s) or coma in a woman with preeclampsia
Number of participants with stroke
New onset neurologic deficit associated with neuroimaging (CT scan or MRI) evidence of brain infarction or bleeding
Initiation of anti-hypertensive medication
Provider documentation of initiation of anti-hypertensive medication (e.g. nifedipine, labetalol)
Pain numerical rating scale (NRS) score
Numerical pain scale score 0-10; 0= no pain and 10=worst possible pain; total score reported
Number of participants with renal failure
Creatinine >1.1 or doubled
Number of participants with pulmonary edema
Evidence of lung infiltrates on chest radiograph or CT scan
Number of participants who die
Length of hospital stay
Number of days from delivery to hospital discharge
Full Information
NCT ID
NCT03824119
First Posted
January 4, 2019
Last Updated
November 4, 2020
Sponsor
University of Southern California
1. Study Identification
Unique Protocol Identification Number
NCT03824119
Brief Title
Postpartum NSAIDS and Maternal Hypertension
Official Title
Effect of Non-steroidal Anti-inflammatory Use on Blood Pressure in Women With Hypertensive Disorders of Pregnancy: A Randomized Open Label Trial
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Unknown status
Study Start Date
December 11, 2018 (Actual)
Primary Completion Date
December 11, 2022 (Anticipated)
Study Completion Date
December 11, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Southern California
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
No
5. Study Description
Brief Summary
Previous studies have suggested that NSAID use causes an increase in blood pressure. Further, blood pressure elevation has been noted in women with pregnancy related hypertensive disease during the postpartum period. NSAIDs remain part of standard postpartum care in women with hypertensive disease. The objective of this study is to determine whether postpartum standard care withholding NSAID use is associated with a clinically significant reduction in postpartum hypertension in women with pregnancy induced hypertension. The investigators hypothesize that women with pregnancy induced hypertensive disease will be half as likely to have blood pressure elevation of 150/100 mmHg in the first 24 hours postpartum.
This study is an open label randomized trial of women with antepartum hypertension. Women will be randomized to receive standard postpartum care or standard postpartum care without NSAIDs. Blood pressure measurements and patient outcomes will be recorded. The study period will begin at the time of delivery and will end at the time of hospital discharge.
Detailed Description
The objective of this study is to determine whether the withholding of NSAID use is associated with a clinically significant decrease in postpartum hypertension in women with antepartum hypertension. The investigators are interested in whether the use of NSAIDs elevates blood pressure to greater than or equal to 150/100 mmHg (by either systolic or diastolic parameters) more frequently in hypertensive women. The investigators hypothesize that among participants with hypertensive disease associated with pregnancy, those who have NSAIDs withheld from standard postpartum care (experimental arm) will be half as likely to have an increase of blood pressure of 150/100 mmHg in the first 24 hours postpartum compared to participants receiving standard care that includes NSAIDs (control arm).
This trial is a randomized, open label study investigating the effect of NSAID use on blood pressure during the immediate postpartum period in women with chronic hypertension (cHTN) or pregnancy induced hypertension (PIH). The experimental group in this study will be women randomized to withholding NSAIDs during the study period, as women with hypertension routinely receive NSAIDs postpartum. Women with a diagnosis of pregnancy induced hypertension [gestational hypertension (gHTN), preeclampsia, superimposed preeclampsia, ] or cHTN will be enrolled antepartum and will be separated into two groups by the route of delivery: vaginal vs. cesarean delivery. Participants in the control arm will be assigned to receive standard care, which includes NSAIDs (ketorolac, ibuprofen) and participants in the experimental arm will be assigned to receive standard care with NSAIDs withheld in the postpartum period for the duration of hospitalization. The intervention period will last approximately 2-4 days and will conclude at the time of hospital discharge.
Blood pressure measurements will be obtained and recorded routinely in the postpartum period until hospital discharge. More frequent measurements may be performed in the event of severe blood pressure elevations at the discretion of the provider and treating clinical team. Complete Blood Count (CBC) on postpartum Day 1 will be performed as part of standard care. Additional laboratory evaluations will be performed at the discretion of the provider. In addition to blood pressure measurement, pain scale scores will be recorded daily using a Numeric Pain Scale Score. Initiation of anti-hypertensive medication, severe hypertension (BP 160/110 mmHg), treatment with magnesium sulfate and adverse maternal outcomes (cerebrovascular accident, congestive heart failure, pulmonary edema, eclamptic seizure, death) will be documented and abstracted from the medical record.
A power calculation to estimate the appropriate number of subjects needed to detect a difference of 30% in the primary outcome, with an alpha level of 0.05 and 80% power demonstrates that approximately 100 subjects per group (50 in the experimental group and 50 in the control group) will be needed for each delivery route tested (vaginal and cesarean).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preeclampsia, Gestational Hypertension, Superimposed Preeclampsia, Chronic Hypertension in Obstetric Context
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard Postpartum Care
Arm Type
Active Comparator
Arm Description
Subjects will receive NSAIDs (e.g. ibuprofen, ketorolac) for routine postpartum pain management.
Arm Title
Standard Postpartum Care without NSAIDs
Arm Type
Active Comparator
Arm Description
Subjects will receive standard postpartum care without NSAID administration for pain management. Acetaminophen or narcotics will be substituted for ibuprofen as indicated by provider.
Intervention Type
Drug
Intervention Name(s)
Ibuprofen 600 mg
Other Intervention Name(s)
Standard Postpartum Care
Intervention Description
Standard postpartum care (including administration of NSAIDs)
Intervention Type
Other
Intervention Name(s)
Standard Postpartum Care without NSAIDs
Intervention Description
NSAID administration will be withheld from this group.
Primary Outcome Measure Information:
Title
Proportion of participants with blood pressure elevation
Description
Incidence of Systolic Blood Pressure of 150 mmHg or Diastolic Blood Pressure of 100 mmHg or above
Time Frame
24 hours postpartum
Secondary Outcome Measure Information:
Title
Proportion of participants with blood pressure elevation
Description
Incidence of Systolic Blood Pressure of 150 mmHg or Diastolic Blood Pressure of 100 mmHg or above
Time Frame
48, 72 and 96 hours postpartum
Title
Number of participants with eclamptic Seizure
Description
Documented occurrence of new onset generalized tonic-clonic seizure(s) or coma in a woman with preeclampsia
Time Frame
Through study completion, up to 6 weeks postpartum
Title
Number of participants with stroke
Description
New onset neurologic deficit associated with neuroimaging (CT scan or MRI) evidence of brain infarction or bleeding
Time Frame
Through study completion, up to 6 weeks postpartum
Title
Initiation of anti-hypertensive medication
Description
Provider documentation of initiation of anti-hypertensive medication (e.g. nifedipine, labetalol)
Time Frame
Randomization through hospital discharge, an average of 3-7 days
Title
Pain numerical rating scale (NRS) score
Description
Numerical pain scale score 0-10; 0= no pain and 10=worst possible pain; total score reported
Time Frame
Randomization through hospital discharge, measured daily, an average of 3-7 days
Title
Number of participants with renal failure
Description
Creatinine >1.1 or doubled
Time Frame
Through study completion, up to 6 weeks postpartum
Title
Number of participants with pulmonary edema
Description
Evidence of lung infiltrates on chest radiograph or CT scan
Time Frame
Through study completion, up to 6 weeks postpartum
Title
Number of participants who die
Time Frame
From the date of randomization through date of death from any cause, assessed up to 6 weeks postpartum
Title
Length of hospital stay
Description
Number of days from delivery to hospital discharge
Time Frame
Through hospital discharge, an average of 3-7 days
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Women 18 years or older delivering at LAC/USC Hospital
Delivery occurring at or after 20 weeks gestation
Diagnosis of antenatal hypertensive disorder: gestational hypertension, preeclampsia without severe features, preeclampsia with severe features, superimposed preeclampsia, eclampsia, chronic hypertension
Exclusion Criteria:
HELLP Syndrome
Renal dysfunction (Serum Creatinine >1.1 in current pregnancy)
Known liver disease
Low platelet count (<50,000 during hospital admission)
Known sensitivity or allergy to ibuprofen or acetaminophen
Use of therapeutic doses of anticoagulation
Postpartum hemorrhage requiring blood transfusion
Neonate with platelet disorder or thrombocytopenia in breastfeeding mother
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elizabeth Sasso, MD
Phone
(323)409-3306
Email
elizabeth.sasso@med.usc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Ian O'Donnell
Phone
(323)409-3306
Email
ian.odonnell@med.usc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Lee, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
LA County Hospital/University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Sasso, MD
Phone
323-409-3306
Email
elizabeth.sasso@med.usc.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
8435027
Citation
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PubMed Identifier
14981414
Citation
Makris A, Thornton C, Hennessy A. Postpartum hypertension and nonsteroidal analgesia. Am J Obstet Gynecol. 2004 Feb;190(2):577-8. doi: 10.1016/j.ajog.2003.08.030.
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Results Reference
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Citation
Viteri OA, England JA, Alrais MA, Lash KA, Villegas MI, Ashimi Balogun OA, Chauhan SP, Sibai BM. Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features. Obstet Gynecol. 2017 Oct;130(4):830-835. doi: 10.1097/AOG.0000000000002247.
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Vigil-De Gracia P, Solis V, Ortega N. Ibuprofen versus acetaminophen as a post-partum analgesic for women with severe pre-eclampsia: randomized clinical study. J Matern Fetal Neonatal Med. 2017 Jun;30(11):1279-1282. doi: 10.1080/14767058.2016.1210599. Epub 2016 Aug 2.
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Results Reference
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Postpartum NSAIDS and Maternal Hypertension
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