Hypertension In Postpartum Preeclampsia Study

Non-steroidal antiinflammatory drugs (NSAIDs) are effective agents for the management of pain in the postpartum period. The addition of NSAIDs to post-cesarean analgesic regimen has been shown to improve post-cesarean pain and reduce opioid requirements. However, concern has been raised over use of NSAIDs in hypertensive pregnant patients, as recent evidence suggests the potential for increased blood pressure in patients with chronic hypertensive disorders receiving these agents. Notably, these studies were conducted on patients with longstanding chronic hypertension, which included males and non-pregnant females, and it is therefore unclear whether this recommendation is appropriate for patients with transient hypertensive disorders of pregnancy.

This protocol describes a randomized trial to evaluate whether NSAIDs influence blood pressure parameters in patients with hypertensive disorders of pregnancy. Patients with severe hypertensive disorders of pregnancy (Severe HDP) will be studied separately from women with mild hypertensive disorders of pregnancy (Mild HDP).

• Acetaminophen (Drug), also known as Tylenol: Participants will receive acetaminophen for postpartum mild pain relief
• Ibuprofen (Drug), also known as Motrin: Participants will receive ibuprofen for postpartum mild pain relief

Primary outcomes

• Average Mean Arterial Blood Pressure- Mild Group [Averaged from all blood pressures measured through study completion, an average of 3 days]: Primary outcome for Hypertensive disorders of pregnancy-Mild Study Group
• Primary Outcome for Hypertensive Disorders of Pregnancy- Severe Study Group [Through study completion, an average of 3 days]: Proportion of participants with at least one episode of severe blood pressure postpartum (systolic >=160 or diastolic >=105mmHg) during inpatient postpartum hospitalization

Secondary outcomes

• Pain Control During Hospital Stay [Through study completion, an average of 3 days]: Wong-Baker Facial Grimace Pain Scale Scores During Inpatient Postpartum Hospital Stay Minimum 0, maximum 10. 10 means the highest level of pain
• Outpatient Blood Pressure Measurement [6 weeks after discharge from the hospital]: Outpatient postpartum blood pressure measurement (represented in mean arterial pressure (MAP) within 6 weeks after discharge
• Patient Satisfaction [Through study completion, an average of 3 days]: Number of patients reporting "High level of satisfaction with pain medications"
• Length of Hospital Stay [Through study completion, an average of 3 days]: Length of Hospital Stay after delivery
• Diuresis [Through study completion, an average of 3 days]: Achievement of average 200ml/hour for 4 consecutive hours
• Average Mean Arterial Blood Pressures During Hospital Stay [Averaged from all blood pressures measured through study completion, an average of 3 days]

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Delivery occurred at equal to or greater than 24 0/7 weeks gestational age
* Patient receiving care with the Women's Perinatal Group (Maternal Fetal Medicine practice) or Obstetric Clinic resident services
* Diagnosis of a hypertensive disorder of pregnancy (HDP), including the following:
* Gestational hypertension
* Preeclampsia without severe features
* Preeclampsia with severe features
* Hemolysis, Elevated Liver Enzymes, Low Platelet (HELLP) Syndrome
* Eclampsia

Exclusion Criteria:

* Diagnosis of chronic hypertension or documentation of elevated blood pressures before 20 weeks gestational age.
* Severe hypertension: Patients with at least one severe blood pressure measurement (systolic >160mmHg or diastolic >105mmHg) prior to randomization
* Renal dysfunction (Serum creatinine measurement >1.3mg/dL during the current pregnancy)
* Low platelet count (recorded measurement <50,000 during hospital admission)
* Significant liver dysfunction (AST or ALT >500)
* Known sensitivities to ibuprofen or acetaminophen
* Use of therapeutic doses of anticoagulation (low dose anticoagulation used for routine prophylaxis of venous thromboembolism is acceptable)
* Postpartum hemorrhage requiring transfusion

Participant flow

Outcome results

• Average Mean Arterial Blood Pressure- Mild Group (Primary), Mean, mmHg: Mild Hypertensive Disorders of Pregnancy- NSAID 93 +/- 8; Mild Hypertensive Disorders of Pregnancy- No NSAID 93 +/- 7
• Primary Outcome for Hypertensive Disorders of Pregnancy- Severe Study Group (Primary), Count of participants, Participants: Severe Hypertensive Disorders of Pregnancy- NSAID 27; Severe Hypertensive Disorders of Pregnancy- No NSAID 29
• Pain Control During Hospital Stay (Secondary), Mean, score on a scale: Severe HDP- NSAID 6.1 +/- 1.5; Mild HDP- NSAID 6.4 +/- 1.4; Severe HDP- No NSAID 5.6 +/- 1.9; Mild HDP- No NSAID 6.0 +/- 1.0
• Outpatient Blood Pressure Measurement (Secondary), Mean, mmHg: Mild HDP- NSAID 99 (89.3 to 108.8); Mild HDP- No NSAID 95 (84.5 to 104.5); Severe HDP-NSAID 97.8 (90.2 to 105.4); Severe HDP-No NSAIDS 102.7 (96.9 to 108.4)
• Patient Satisfaction (Secondary), Count of participants, Participants: Severe HDP- NSAID 58; Mild HDP- NSAID 22; Severe HDP- No NSAID 65; Mild HDP- No NSAID 22
• Length of Hospital Stay (Secondary), Median, days: Severe HDP- NSAID 4.3 (1.9 to 6.7); Mild HDP- NSAID 2.0 (1.71 to 2.3); Severe HDP- No NSAID 3.7 (2.7 to 4.7); Mild HDP- No NSAID 1.8 (1.56 to 1.95)
• Diuresis (Secondary), Count of participants, Participants: Severe HDP- NSAID 45; Mild HDP- NSAID 19; Severe HDP- No NSAID 46; Mild HDP- No NSAID 23
• Average Mean Arterial Blood Pressures During Hospital Stay (Secondary), Mean, mmHG: Severe Hypertensive Disorders of Pregnancy- NSAID 95.7 +/- 8.2; Severe Hypertensive Disorders of Pregnancy- No NSAID 95.9 +/- 9.5

Adverse events

Time frame: Adverse event data was collected from study enrollment until 6 weeks postpartum.

• Results publication: Penfield CA, McNulty JA, Oakes MC, Nageotte MP. Ibuprofen and Postpartum Blood Pressure in Women With Hypertensive Disorders of Pregnancy: A Randomized Controlled Trial. Obstet Gynecol. 2019 Dec;134(6):1219-1226. doi: 10.1097/AOG.0000000000003553. PMID 31764732

• Study Protocol and Statistical Analysis Plan (PDF, 2016-10-13)

• Jennifer McNulty, MD, Principal investigator, Long Beach Memorial Medical Center