Clinical trial NCT02911701: Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
Official title: Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pre-Eclampsia
HELLP Syndrome
Eclampsia
Lead sponsor: University of New Mexico
Sponsor class: OTHER
First posted: 2016-09-22
Enrollment: 100
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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Duration of Severe-range Hypertension After Delivery
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
Secondary outcomes:
measure: Length of Hospitalization
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Mean Arterial Pressure Over the Entire Postpartum Hospitalization
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Mean Arterial Pressure, Stratified by Postpartum Day 1, 2, 3, Etc.
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Mean Total Number of Severe Range Blood Pressure Measurements in Each Study Arm.
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Proportion of Study Participants in Each Study Arm Who Have Any Postpartum Severe Range BPs
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Mean Maximum Measured Blood Pressure for Entire Postpartum Hospitalization (in mm Hg)
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Proportion of Study Participants Requiring the Use of Scheduled Oral Antihypertensives at Discharge
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Number of Scheduled Oral Antihypertensive Agents Required at Discharge
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Need for Antihypertensives (Either Oral or Intravenous) for Acute Lowering of Blood Pressure
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: The Proportion of Study Participants Requiring the Use of Intravenous Antihypertensives
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Mean Daily Pain Level, as Reported by Patient on Scale From 1-10, Stratified by Postpartum Day
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Use of Opioid Analgesics, Measured in Morphine Milligram Equivalents Per Day, Stratified by Postpartum Day
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Serum Creatinine Trend From Day of Delivery to Day of Discharge
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Mean Drop in Hematocrit From Pre-delivery to the Nadir Prior to Discharge
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Composite of Adverse Events
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Proportion of Study Participants in Each Study Arm With New Onset Postpartum Elevation of Liver Function Tests (AST, ALT) Above Twice the Normal Limit
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Proportion of Study Participants in Each Study Arm With New Onset Postpartum Acute Kidney Injury
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
measure: Proportion of Study Participants in Each Study Arm With Delayed Postpartum Hemorrhage
timeFrame: duration of postpartum hospitalization (approximately 3-7 days)
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
Study officials:
affiliation: University of New Mexico
name: Luis Izquierdo, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References: