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

Preeclampsia Severe Clinical Trial

— PANDA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03978767
• Other study ID #: 201901202
• Status: Recruiting
• Phase: Phase 2
• Start date: June 10, 2019
• Est. completion date: June 1, 2025

Study information

• Verified date: April 2024
• Source: Washington University School of Medicine
• Contact: Jonathan S Hirshberg, MD
• Phone: 314-362-5000
• Email: jhirshberg[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 286
• Est. completion date: June 1, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Pre-Eclampsia
• Preeclampsia Postpartum
• Preeclampsia Severe

Intervention

Drug:
• Ibuprofen 600 mg
NSAID pain medication to be used in the experimental bundle for postpartum analgesia
• Ketorolac
NSAID analgesic to be used in the experimental bundle for postpartum analgesia in patients who underwent cesarean section
• Acetaminophen
Analgesic medication to be used in both treatment arms
• Oxycodone
Analgesic medication to be used in both treatment arms

Locations

Country	Name	City	State
United States	Barnes Jewish Hospital	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	postpartum antihypertensive requirements	measurement of anti-hypertensive requirements at time of discharge	at the end of hospitalization, up to 7 days after randomization
Secondary	Postpartum pain scores	Evaluate the effect of NSAIDs on patient perception of pain	From randomization to 6 weeks after randomization
Secondary	Postpartum opioid use	Compare the opioid requirements in each arm	From randomization to 6 weeks after randomization
Secondary	Mean arterial blood pressure	Compare peak, average and median MAPs postpartum	From randomization to 6 weeks after randomization
Secondary	End organ damage	Evaluate for evidence of renal, hepatic or neurological injury in the poatpartum period	during hospitalization, an average of 4 days
Secondary	Hospital readmission	Evaluate the incidence of hospital readmission rate postpartum	From randomization to 6 weeks after randomization
Secondary	Continued anti-hypertensive requirement	evaluate the need for antihypertensive medications at 6 weeks postpartum	up to 6 weeks