Clinical trial NCT03978767: Preeclampsia And Nonsteroidal Drugs for Analgesia: a Randomized Non Inferiority Trial
Official title: Preeclampsia And Nonsteroidal Drugs for Analgesia (PANDA): a Randomized Non Inferiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Preeclampsia Severe
Preeclampsia Postpartum
Keywords: NSAIDs
Ibuprofen
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2019-06-07
Enrollment: 286
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized non-inferiority clinical trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: postpartum antihypertensive requirements
timeFrame: at the end of hospitalization, up to 7 days after randomization
Secondary outcomes:
measure: Postpartum pain scores
timeFrame: From randomization to 6 weeks after randomization
measure: Postpartum opioid use
timeFrame: From randomization to 6 weeks after randomization
measure: Mean arterial blood pressure
timeFrame: From randomization to 6 weeks after randomization
measure: End organ damage
timeFrame: during hospitalization, an average of 4 days
measure: Hospital readmission
timeFrame: From randomization to 6 weeks after randomization
measure: Continued anti-hypertensive requirement
timeFrame: up to 6 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
Study officials:
References:
citation: Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88. No abstract available.
citation: Lo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013 Apr;25(2):124-32. doi: 10.1097/GCO.0b013e32835e0ef5.
citation: Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005 Feb 26-Mar 4;365(9461):785-99. doi: 10.1016/S0140-6736(05)17987-2.
citation: Mogos MF, Salemi JL, Spooner KK, McFarlin BL, Salihu HH. Hypertensive disorders of pregnancy and postpartum readmission in the United States: national surveillance of the revolving door. J Hypertens. 2018 Mar;36(3):608-618. doi: 10.1097/HJH.0000000000001594.
citation: Viteri OA, England JA, Alrais MA, Lash KA, Villegas MI, Ashimi Balogun OA, Chauhan SP, Sibai BM. Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features. Obstet Gynecol. 2017 Oct;130(4):830-835. doi: 10.1097/AOG.0000000000002247.