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

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ClinicalTrials.gov Identifier: NCT02891174
Recruitment Status : Completed
First Posted : September 7, 2016
Results First Posted : May 23, 2019
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
Elizabeth Langen, University of Michigan

Tracking Information
First Submitted Date  ICMJE August 26, 2016
First Posted Date  ICMJE September 7, 2016
Results First Submitted Date  ICMJE March 19, 2019
Results First Posted Date  ICMJE May 23, 2019
Last Update Posted Date May 23, 2019
Actual Study Start Date  ICMJE December 1, 2016
Actual Primary Completion Date March 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
Difference in Systolic Blood Pressure (SBP) [ Time Frame: 24 hours following intervention ]
The adjusted mean difference in systolic blood pressure after 24 hours of exposure each to ibuprofen and acetaminophen.
Original Primary Outcome Measures  ICMJE
 (submitted: August 31, 2016)
Mean difference in systolic blood pressure (SBP) during 24 hours of exposure each to ibuprofen and acetaminophen [ Time Frame: Immediately post-partum, 24 hours post-partum, and 48 hours post-partum ]
To determine the difference in SBP from baseline (immediately post-partum) during 24 hours of drug exposure each to ibuprofen and acetaminophen. Baseline SBP will be calculated as the arithmetic mean of the initial 5 blood pressures recorded after admission for labor or induction of labor. Standard blood pressure monitoring per post-partum protocol: every 15 minutes for 1 hour, then every 30 min for 1 hour, then every 4-8 hours until discharge per the discretion of the treating team. The primary hypothesis is that of equivalence.
Change History Complete list of historical versions of study NCT02891174 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
  • Change in Self-reported Pain Score 2 Hours After First Intervention [ Time Frame: At the time of first dose of study drug and 2 hours after ]
    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.
  • Mean Pain Score by Nursing Assessment [ Time Frame: 0-24 hours and 24-48 hours after initial study medication administration ]
    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.
  • Satisfaction With Pain Control During 24 Hours of Exposure Each to Ibuprofen and Acetaminophen [ Time Frame: 24 hours and 48 hours after initial study medication administration ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2016)
  • Change in pain score during immediate post-partum period [ Time Frame: 48 hours from initial study medication administration ]
    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. Pain scores as assessed by nursing during the 48 hours from initial study medication administration will also be abstracted from the participant's medical record.
  • Satisfaction With Pain Control During 24 Hours of Exposure Each to Ibuprofen and Acetaminophen [ Time Frame: 24 hours and 48 hours after initial study medication administration ]
    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 scale.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
Official Title  ICMJE A Randomized-controlled Trial to Assess the Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypertension, Pregnancy-Induced
  • Pre-eclampsia
Intervention  ICMJE
  • 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 Name: Tylenol
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Ibuprofen
    • Drug: Acetaminophen
  • 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.
    Interventions:
    • Drug: Ibuprofen
    • Drug: Acetaminophen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 28, 2018)
74
Original Estimated Enrollment  ICMJE
 (submitted: August 31, 2016)
40
Actual Study Completion Date  ICMJE June 20, 2018
Actual Primary Completion Date March 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02891174
Other Study ID Numbers  ICMJE HUM00117154
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Elizabeth Langen, University of Michigan
Study Sponsor  ICMJE University of Michigan
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jourdan Triebwasser, MD University of Michigan
Principal Investigator: Elizabeth Langen, MD University of Michigan
Principal Investigator: Alexander Tsodikov, PhD University of Michigan
PRS Account University of Michigan
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP