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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02911701

Enrollment

100

Registered

2016-09-22

Start date

2016-09-30

Completion date

2018-01-10

Last updated

2023-07-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Eclampsia, HELLP Syndrome, Pre-Eclampsia

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.

Interventions

DRUGAcetaminophen

DRUGIbuprofen

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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 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 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
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	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
Length of Hospitalization	duration of postpartum hospitalization (approximately 3-7 days)	number of days from delivery until hospital discharge
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).
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	duration of postpartum hospitalization (approximately 3-7 days)	Mean difference in hematocrit from pre-delivery to postpartum nadir prior to discharge
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.
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 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
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
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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Acetaminophen Study participants randomized to the acetaminophen group will receive 650mg of acetaminophen orally every 6 hours during their postpartum hospital stay. Acetaminophen	50
Ibuprofen Study participants randomized to the ibuprofen group will receive 600mg of ibuprofen orally every 6 hours during their postpartum hospital stay. Ibuprofen	50
Total	100

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Withdrawal by Subject	2	4

Baseline characteristics

Characteristic	Total	Ibuprofen	Acetaminophen
Age, Continuous	31.2 years STANDARD_DEVIATION 6.1	31.9 years STANDARD_DEVIATION 5.9	30.5 years STANDARD_DEVIATION 6.4
chronic hypertension requiring treatment	15 Participants	8 Participants	7 Participants
mode of delivery Cesarean	41 Participants	24 Participants	17 Participants
mode of delivery Operative vaginal	2 Participants	1 Participants	1 Participants
mode of delivery Vaginal	57 Participants	25 Participants	32 Participants
need for IV Antihypertensives before delivery	79 Participants	42 Participants	37 Participants
Parity Multiparous	63 Participants	32 Participants	31 Participants
Parity Nulliparous	37 Participants	18 Participants	19 Participants
Race/Ethnicity, Customized Race/ethnicity Asian	2 Participants	2 Participants	0 Participants
Race/Ethnicity, Customized Race/ethnicity Black	3 Participants	2 Participants	1 Participants
Race/Ethnicity, Customized Race/ethnicity Hispanic	40 Participants	20 Participants	20 Participants
Race/Ethnicity, Customized Race/ethnicity Native American	21 Participants	9 Participants	12 Participants
Race/Ethnicity, Customized Race/ethnicity Other	10 Participants	6 Participants	4 Participants
Race/Ethnicity, Customized Race/ethnicity White	24 Participants	11 Participants	13 Participants
Region of Enrollment United States	100 Participants	50 Participants	50 Participants
Sex: Female, Male Female	100 Participants	50 Participants	50 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 50	0 / 50
other Total, other adverse events	0 / 50	0 / 50
serious Total, serious adverse events	1 / 50	3 / 50