Clinical trial NCT02891174: The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
Official title: A Randomized-controlled Trial to Assess the Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension, Pregnancy-Induced
Pre-eclampsia
Keywords: ibuprofen
acetaminophen
blood pressure
post-partum
pain control
pre-eclampsia
gestational hypertension
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2016-09-07
Enrollment: 74
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference in Systolic Blood Pressure (SBP)
timeFrame: 24 hours following intervention
Secondary outcomes:
measure: Change in Self-reported Pain Score 2 Hours After First Intervention
timeFrame: At the time of first dose of study drug and 2 hours after
measure: Mean Pain Score by Nursing Assessment
timeFrame: 0-24 hours and 24-48 hours after initial study medication administration
measure: Satisfaction With Pain Control During 24 Hours of Exposure Each to Ibuprofen and Acetaminophen
timeFrame: 24 hours and 48 hours after initial study medication administration
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Jourdan Triebwasser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Elizabeth Langen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Alexander Tsodikov, PhD
role: PRINCIPAL_INVESTIGATOR
References: