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Preeclampsia And Nonsteroidal Drugs for Analgesia: a Randomized Non Inferiority Trial

Phase 2
Recruiting
Conditions
Preeclampsia Severe
Preeclampsia Postpartum
Interventions
Registration Number
NCT03978767
Lead Sponsor
Washington University School of Medicine
Brief Summary

A randomized non-inferiority trial of women with preeclampsia with severe features to determine if the addition of nonsteroidal anti-inflammatory drugs is inferior or non-inferior to standard analgesic bundles in their impact on postpartum hypertension.

Detailed Description

Recently published clinical guidelines for the care of women with hypertensive disorders recommended that nonsteroidal anti-inflammatory drugs (NSAIDs) should be withheld from patients with hypertension that persists for more than one day postpartum (1). This recommendation is based in data from the general medicine literature, which suggests a role of NSAIDs in precipitating hypertension in non-pregnant adults (2,3). It may also draw from previously published case reports of post-partum hypertension that were thought to be NSAID induced (4). There has been a paucity of data from the obstetric literature to support or rebuff this recommendation. As the opioid crisis worsens in the United States, additional attention and resources have focused on limiting the use of narcotic medications. The effective employment of non-opioid analgesics has been shown to reduce narcotic use (5). Ibuprofen and other NSAIDs are the most effective and most commonly prescribed analgesics for postpartum pain, but clinicians now find themselves stuck between these recommendations and their efforts to limit unnecessary opioid prescriptions.

The investigators propose a randomized controlled non-inferiority trial of women with preeclampsia comparing a postpartum analgesic protocol that includes NSAIDs, to one that excludes them. The central hypothesis is that NSAID use does not worsen hypertensive diseases of pregnancy.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
286
Inclusion Criteria
  • Women at > 23 weeks gestational age undergoing vaginal or cesarean delivery at Barnes-Jewish Hospital with:
  • An antepartum diagnosis of preeclampsia with severe features
  • Pre-eclampsia with severe features will be defined as:
  • Elevated blood pressure ≥ 160/110, or
  • Pre-eclampsia in the setting of thrombocytopenia (platelet count < 100,000), or
  • Impaired liver function (AST elevated to twice upper limit of normal), or
  • Persistent epigastric pain, or
  • Renal insufficiency (serum creatinine of 1.1 mg/dl or doubling of prior value), or
  • Pulmonary edema, or
  • New onset visual disturbance or headache unresponsive to therapy.
Exclusion Criteria
  • NSAID allergy
  • Allergy to acetaminophen
  • Antihypertensive use in this pregnancy prior to 20 weeks gestation
  • Chronic kidney disease or Acute kidney injury with Creatine clearance less than 60 mL/min
  • Inability to obtain consent
  • Opioid abuse disorder
  • Peptic ulcer disease.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NSAID free analgesic bundleOxycodoneAcetaminophen 1000mg q 8 hrs as needed for pain, and Oxycodone 5 to 10 mg q 4 hrs as needed for pain.
NSAID Analgesic bundleIbuprofen 600 mgIbuprofen 600mg PO q 6 hrs as needed for pain, Acetaminophen 1000mg q 8 hrs as needed for pain, and Oxycodone 5 to 10 mg q 4 hrs as needed for pain. In patients undergoing cesarean section, ketorolac 30mg IV q 6 hrs may be substituted as an IV alternative to ibuprofen for the first 24 hours after surgery
NSAID free analgesic bundleAcetaminophenAcetaminophen 1000mg q 8 hrs as needed for pain, and Oxycodone 5 to 10 mg q 4 hrs as needed for pain.
NSAID Analgesic bundleKetorolacIbuprofen 600mg PO q 6 hrs as needed for pain, Acetaminophen 1000mg q 8 hrs as needed for pain, and Oxycodone 5 to 10 mg q 4 hrs as needed for pain. In patients undergoing cesarean section, ketorolac 30mg IV q 6 hrs may be substituted as an IV alternative to ibuprofen for the first 24 hours after surgery
NSAID Analgesic bundleAcetaminophenIbuprofen 600mg PO q 6 hrs as needed for pain, Acetaminophen 1000mg q 8 hrs as needed for pain, and Oxycodone 5 to 10 mg q 4 hrs as needed for pain. In patients undergoing cesarean section, ketorolac 30mg IV q 6 hrs may be substituted as an IV alternative to ibuprofen for the first 24 hours after surgery
NSAID Analgesic bundleOxycodoneIbuprofen 600mg PO q 6 hrs as needed for pain, Acetaminophen 1000mg q 8 hrs as needed for pain, and Oxycodone 5 to 10 mg q 4 hrs as needed for pain. In patients undergoing cesarean section, ketorolac 30mg IV q 6 hrs may be substituted as an IV alternative to ibuprofen for the first 24 hours after surgery
Primary Outcome Measures
NameTimeMethod
postpartum antihypertensive requirementsat the end of hospitalization, up to 7 days after randomization

measurement of anti-hypertensive requirements at time of discharge

Secondary Outcome Measures
NameTimeMethod
End organ damageduring hospitalization, an average of 4 days

Evaluate for evidence of renal, hepatic or neurological injury in the poatpartum period

Postpartum pain scoresFrom randomization to 6 weeks after randomization

Evaluate the effect of NSAIDs on patient perception of pain

Hospital readmissionFrom randomization to 6 weeks after randomization

Evaluate the incidence of hospital readmission rate postpartum

Postpartum opioid useFrom randomization to 6 weeks after randomization

Compare the opioid requirements in each arm

Mean arterial blood pressureFrom randomization to 6 weeks after randomization

Compare peak, average and median MAPs postpartum

Continued anti-hypertensive requirementup to 6 weeks

evaluate the need for antihypertensive medications at 6 weeks postpartum

Trial Locations

Locations (1)

Barnes Jewish Hospital

🇺🇸

Saint Louis, Missouri, United States

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