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

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.

Study Overview

• Status: Completed
• Conditions: Eclampsia; Pre-Eclampsia; HELLP Syndrome
• Intervention / Treatment: Drug: Ibuprofen; Drug: Acetaminophen

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States
      • University of New Mexico Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetaminophen; Study participants randomized to the acetaminophen group will receive 650mg of acetaminophen orally every 6 hours during their postpartum hospital stay.	Drug: Acetaminophen; Other Names: Tylenol
Active Comparator: Ibuprofen; Study participants randomized to the ibuprofen group will receive 600mg of ibuprofen orally every 6 hours during their postpartum hospital stay.	Drug: Ibuprofen; Other Names: Motrin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of New Mexico
• Investigators: Principal Investigator: Luis Izquierdo, MD, MBA, University of New Mexico

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): November 7, 2017
• Study Completion (Actual): January 10, 2018

Study Registration Dates

• First Submitted: September 9, 2016
• First Submitted That Met QC Criteria: September 19, 2016
• First Posted (Estimated): September 22, 2016

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Eclampsia; Pre-Eclampsia; HELLP Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Acetaminophen; Ibuprofen
• Other Study ID Numbers: 16-147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO