Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features

Phase 4

Completed

Conditions: HELLP Syndrome
Eclampsia
Pre-Eclampsia

Interventions: Drug: Ibuprofen
Drug: Acetaminophen

Registration Number: NCT02911701

Lead Sponsor: University of New Mexico

Brief Summary: NSAIDs, specifically cyclo-oxygenase (COX) inhibitors, are known to increase blood pressure over time in non-pregnant adults, but the effect of COX-inhibitors on blood pressure in the setting of preeclampsia have not been well studied. This study aims to assess the effect of avoiding COX-inhibitors on postpartum blood pressure control among women diagnosed with preeclampsia with severe features. Eligible women will be randomized to receive either acetaminophen or ibuprofen for postpartum pain control. Both agents are first line therapies for pain control although ibuprofen has better pain control than acetaminophen. The primary outcome will be duration of postpartum severe-range hypertension.

Detailed Description: The proposed study is a randomized, controlled, double-masked trial comparing the effect of postpartum acetaminophen and ibuprofen on blood pressure among women with preeclampsia. Study participants will be randomized to receive either acetaminophen or ibuprofen for mild postpartum pain control. Study participants, study personnel and providers will be blinded to randomization status of study participants.

Potential study participants will be enrolled when they are diagnosed with a severe hypertensive disorder of pregnancy. This will usually occur prior to delivery, but may occur up to 6 hours after delivery. Patients diagnosed with preeclampsia without severe features will also be approached and enrolled at the time of diagnosis in anticipation for possible progression to preeclampsia with severe features. Once enrolled, study participants will not be randomized until delivery, at which time they will be randomized to receive either acetaminophen or ibuprofen for mild postpartum pain. Both groups will have available oxycodone for moderate to severe pain, per our routine. Study group allocation will only be known by the investigational pharmacy. The ibuprofen and acetaminophen will be made to appear identical to each other and will be unmarked through encapsulation. Block randomization will be used to ensure equal allocation to the two study arms.

For the duration of study participation, study participants will undergo postpartum monitoring with vital sign measurements (including blood pressure) every 4 hours, pain assessment with each administration of study medication, as well as daily evaluation of laboratory studies until they have normalized to the satisfaction of their provider. Study participants will receive the study drug every 6 hours from the time of delivery until hospital discharge, unless they refuse. Study participation will be complete upon hospital discharge. Study participants will be contacted by a study team member 6 weeks after delivery to ask about any additional complications or symptoms requiring visits to the emergency department or hospital readmission. Descriptive factors and clinical outcomes will be extracted from the medical record and de-identified by study personnel during each day of study participation.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 100

Inclusion Criteria

ability to give informed consent
diagnosis of a "severe" hypertensive disorder of pregnancy:
preeclampsia with severe features
chronic hypertension with superimposed preeclampsia with severe features
HELLP syndrome: hemolysis, elevated liver function tests, low platelets
eclampsia
not yet delivered or less than 6 hours after delivery

Exclusion Criteria

current incarceration
serum creatinine > 1.0 mg/dL or suspicion of acute kidney injury
AST (aspartate aminotransferase) >200 unit/L
ALT (alanine aminotransferase) > 200 unit/L
known allergy or sensitivity to NSAIDs or acetaminophen
delivery > 6 hours prior to enrollment
chronic kidney disease
chronic liver disease
prior liver transplant
chronic infectious hepatitis
gastritis
gastro-esophageal reflux disease (GERD)
peptic ulcer disease
bleeding disorder
provider feels that participation is not in the best interest of the patient

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ibuprofen	Ibuprofen	Study participants randomized to the ibuprofen group will receive 600mg of ibuprofen orally every 6 hours during their postpartum hospital stay.
Acetaminophen	Acetaminophen	Study participants randomized to the acetaminophen group will receive 650mg of acetaminophen orally every 6 hours during their postpartum hospital stay.

Primary Outcome Measures

Name	Time	Method
Duration of Severe-range Hypertension After Delivery	duration of postpartum hospitalization (approximately 3-7 days)	length of time from delivery to the last severe range blood pressure (160/110mm Hg) measured

Secondary Outcome Measures

Name	Time	Method
Mean Arterial Pressure Over the Entire Postpartum Hospitalization	duration of postpartum hospitalization (approximately 3-7 days)	computed mean arterial pressure using all measured blood pressures during postpartum hospitalization
Proportion of Study Participants in Each Study Arm Who Have Any Postpartum Severe Range BPs	duration of postpartum hospitalization (approximately 3-7 days)	Severe-range hypertension (defined as SBP \> 160 mmHg or DBP \>1100 mmHg) during postpartum stay
Composite of Adverse Events	duration of postpartum hospitalization (approximately 3-7 days)	Adverse events include seizure, stroke, posterior reversible encephalopathy syndrome, repeat course of IV magnesium sulfate for seizure prophylaxis.
Mean Arterial Pressure, Stratified by Postpartum Day 1, 2, 3, Etc.	duration of postpartum hospitalization (approximately 3-7 days)	computed mean arterial pressure using all measured blood pressures during postpartum hospitalization, stratified by postpartum day (1, 2, 3, etc.)
Mean Maximum Measured Blood Pressure for Entire Postpartum Hospitalization (in mm Hg)	duration of postpartum hospitalization (approximately 3-7 days)
Serum Creatinine Trend From Day of Delivery to Day of Discharge	duration of postpartum hospitalization (approximately 3-7 days)
Proportion of Study Participants in Each Study Arm With New Onset Postpartum Acute Kidney Injury	duration of postpartum hospitalization (approximately 3-7 days)	Acute kidney injury is defined as serum creatinine \> 1.1mg/dL or double the baseline value
Length of Hospitalization	duration of postpartum hospitalization (approximately 3-7 days)	number of days from delivery until hospital discharge
Need for Antihypertensives (Either Oral or Intravenous) for Acute Lowering of Blood Pressure	duration of postpartum hospitalization (approximately 3-7 days)	Proportion in each arm who required one or more doses of antihypertensive medication given for acute lowering of BP
The Proportion of Study Participants Requiring the Use of Intravenous Antihypertensives	duration of postpartum hospitalization (approximately 3-7 days)	The proportion of study participants in each study arm who require any IV antihypertensives to acutely lower blood pressure during their postpartum hospital stay.
Use of Opioid Analgesics, Measured in Morphine Milligram Equivalents Per Day, Stratified by Postpartum Day	duration of postpartum hospitalization (approximately 3-7 days)
Mean Total Number of Severe Range Blood Pressure Measurements in Each Study Arm.	duration of postpartum hospitalization (approximately 3-7 days)	mean total number of severe range blood pressure (defined as SBP \>160mmGh or DBP \>110mmHg) measurements in each study arm
Proportion of Study Participants Requiring the Use of Scheduled Oral Antihypertensives at Discharge	duration of postpartum hospitalization (approximately 3-7 days)
Number of Scheduled Oral Antihypertensive Agents Required at Discharge	duration of postpartum hospitalization (approximately 3-7 days)
Mean Daily Pain Level, as Reported by Patient on Scale From 1-10, Stratified by Postpartum Day	duration of postpartum hospitalization (approximately 3-7 days)	Mean daily pain level, as reported by patient on scale from 1-10 (10 is most severe).
Mean Drop in Hematocrit From Pre-delivery to the Nadir Prior to Discharge	duration of postpartum hospitalization (approximately 3-7 days)	Mean difference in hematocrit from pre-delivery to postpartum nadir prior to discharge
Proportion of Study Participants in Each Study Arm With New Onset Postpartum Elevation of Liver Function Tests (AST, ALT) Above Twice the Normal Limit	duration of postpartum hospitalization (approximately 3-7 days)	AST: Aspartate aminotransferase; ALT: alanine aminotransferase
Proportion of Study Participants in Each Study Arm With Delayed Postpartum Hemorrhage	duration of postpartum hospitalization (approximately 3-7 days)	Delayed postpartum hemorrhage is defined as \> 1000 mL of blood loss occuring \> 24 hours after delivery