The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy

A Randomized-controlled Trial to Assess the Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy

To assess the effect of routine doses of ibuprofen on post-partum blood pressure control in women with gestational hypertension (gHTN) or preeclampsia without severe features (preE).

Study Overview

• Status: Completed
• Conditions: Hypertension, Pregnancy-Induced; Pre-eclampsia
• Intervention / Treatment: Drug: Ibuprofen; Drug: Acetaminophen

Detailed Description

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for post-partum analgesia. This use is supported by limited data on post-partum pain specifically; however, ibuprofen and other NSAIDs are superior to acetaminophen in ameliorating uterine pain and cramping in dysmenorrhea. The effect of NSAIDs on blood pressure (BP) in women post-partum is less well-known. In non-pregnant hypertensive patients NSAIDs are associated with increased BP over short courses of days to months, though effects of various NSAIDs differ. Pooled analyses suggest changes in mean BP of up to 3-6 mm Hg depending on the measurement method.There are case reports of hypertensive crises after NSAID administration post-partum in both normotensive and hypertensive women. A larger, recent retrospective cohort study found no difference in mean arterial pressure (MAP) or need for antihypertensive therapy in women with severe hypertensive disorders of pregnancy who were exposed to NSAIDs post-partum.

In light of the potential for worsening blood pressure in women with hypertensive disorders of pregnancy, the Task Force on Hypertension in Pregnancy of American College of Obstetricians and Gynecologists stated that "providers should be reminded of the contribution of nonsteroidal anti-inflammatory agents to increased BP." Additionally the task force recommends that NSAIDS "be replaced by other analgesics in women with hypertension that persists for more than 1 day postpartum". However, provider practices since the publication of these guidelines have varied.

Hypothesis: When compared to acetaminophen, ibuprofen does not increase post-partum systolic blood pressure (SBP) above baseline to a clinically relevant degree (≥10 mmHg) in women with gHTN and preE.

Aim 1: To assess the mean difference in SBP during 24 hours of exposure to ibuprofen and acetaminophen.

Aim 2: To assess whether ibuprofen results in higher satisfaction with pain control in the immediate post-partum period (48 hours) compared to acetaminophen.

Aim 3: To prospectively assess the need for post-partum anti-hypertensive therapy and readmission for blood pressure control in women with gHTN and preE. The post-partum period is defined as delivery through 6 weeks after delivery.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Antepartum women
• Diagnosis of Gestational Hypertension or Pre-eclampsia by blood pressure ≥140 systolic or ≥90 diastolic, on at least 2 measurements ≥ 4 hours apart; with or without proteinuria (urine protein-creatinine ratio ≥0.3 or 24 hour-urine protein ≥300 mg).
• Taking one or fewer oral medications for blood pressure control.
• Singleton gestation.
• English-speaking

Exclusion Criteria:

• Allergy to nonsteroidal anti-inflammatory drugs, aspirin, or acetaminophen
• More than 1 severe range blood pressure (≥160 systolic or ≥110 diastolic) prior to enrollment.
• Neurologic symptoms attributed to hypertension (headache, visual changes) prior to enrollment.
• Pulmonary edema.
• Elevated AST (>60 international units/L) or ALT (>70 international units/L) prior to enrollment.
• Low platelet count (<100,000/microliter) prior to enrollment.
• Renal insufficiency (creatinine > 1.1 or double the baseline creatinine if known) prior to enrollment.
• Chronic hypertension defined as hypertension pre-existing pregnancy or diagnosed prior to 20-weeks' gestation.
• Moderate- or severe-persistent asthma.
• Therapeutic anticoagulation.
• Chronic opiate use during the pregnancy (opiate therapy given daily for > 2 weeks).
• Lactose intolerance or allergy due to placebo containing lactose.
• Cesarean delivery.
• Additional anesthesia at time of delivery (spinal anesthesia, sedation) that would change routine pain management.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ibuprofen followed by acetaminophen; Ibuprofen administered immediately post-partum, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours followed by acetaminophen, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours.	Drug: Ibuprofen; At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with ibuprofen followed by acetaminophen.; Other Names: Advil; Motrin; Drug: Acetaminophen; At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with acetaminophen followed by ibuprofen.; Other Names: Tylenol
Active Comparator: Acetaminophen followed by ibuprofen; Acetaminophen administered immediately post-partum, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours followed by ibuprofen, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours.	Drug: Ibuprofen; At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with ibuprofen followed by acetaminophen.; Other Names: Advil; Motrin; Drug: Acetaminophen; At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with acetaminophen followed by ibuprofen.; Other Names: Tylenol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Systolic Blood Pressure (SBP)	The adjusted mean difference in systolic blood pressure after 24 hours of exposure each to ibuprofen and acetaminophen.	24 hours following intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Self-reported Pain Score 2 Hours After First Intervention	Prior to the first dose of pain medication, participants will take a brief, self-administered survey to assess abdominal and overall pain using a 0-10 scale. Two hours after the first dose of study drug, participants will repeat the self-administered survey to assess abdominal, perineal, and overall pain using a 0-10 scale. Clinical Pain Scale: 0=no pain to 10=worst pain.	At the time of first dose of study drug and 2 hours after
Mean Pain Score by Nursing Assessment	Pain scores using a 0-10 scale as assessed by nursing during the 48 hours from initial study medication administration will be abstracted from the participant's medical record. Clinical Pain Scale: 0=no pain to 10=worst pain. All pain scores during the first intervention (0-24 hours) and second intervention (24-48) are included according to intention-to-treat principles.	0-24 hours and 24-48 hours after initial study medication administration
Satisfaction With Pain Control During 24 Hours of Exposure Each to Ibuprofen and Acetaminophen	A brief survey on satisfaction with pain control during the first 24 hours post-partum and the second 24 hours post-partum, as well as overall during post-partum stay will be administered prior to discharge using a 1-5 Likert scale: 1=not satisfied to 5=extremely satisfied.	24 hours and 48 hours after initial study medication administration

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Jourdan Triebwasser, MD, University of Michigan; Principal Investigator: Elizabeth Langen, MD, University of Michigan; Principal Investigator: Alexander Tsodikov, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): March 31, 2018
• Study Completion (Actual): June 20, 2018

Study Registration Dates

• First Submitted: August 26, 2016
• First Submitted That Met QC Criteria: August 31, 2016
• First Posted (Estimate): September 7, 2016

Study Record Updates

• Last Update Posted (Actual): May 23, 2019
• Last Update Submitted That Met QC Criteria: May 3, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: acetaminophen; ibuprofen; blood pressure; pre-eclampsia; pain control; gestational hypertension; post-partum
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Infections; Pregnancy Complications; Toxemia; Hypertension; Eclampsia; Pre-Eclampsia; Hypertension, Pregnancy-Induced; 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: HUM00117154

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• 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