Clinical trial NCT03824119: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Preeclampsia
Gestational Hypertension
Superimposed Preeclampsia
Chronic Hypertension in Obstetric Context
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2019-01-31
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Proportion of participants with blood pressure elevation
timeFrame: 24 hours postpartum
Secondary outcomes:
measure: Proportion of participants with blood pressure elevation
timeFrame: 48, 72 and 96 hours postpartum
measure: Number of participants with eclamptic Seizure
timeFrame: Through study completion, up to 6 weeks postpartum
measure: Number of participants with stroke
timeFrame: Through study completion, up to 6 weeks postpartum
measure: Initiation of anti-hypertensive medication
timeFrame: Randomization through hospital discharge, an average of 3-7 days
measure: Pain numerical rating scale (NRS) score
timeFrame: Randomization through hospital discharge, measured daily, an average of 3-7 days
measure: Number of participants with renal failure
timeFrame: Through study completion, up to 6 weeks postpartum
measure: Number of participants with pulmonary edema
timeFrame: Through study completion, up to 6 weeks postpartum
measure: Number of participants who die
timeFrame: From the date of randomization through date of death from any cause, assessed up to 6 weeks postpartum
measure: Length of hospital stay
timeFrame: Through hospital discharge, an average of 3-7 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: LA County Hospital/University of Southern California
state: California
Study officials:
affiliation: University of Southern California
name: Richard Lee, MD
role: PRINCIPAL_INVESTIGATOR
References:
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