NSAIDs for Preeclampsia

(PANDA Trial)

Overseen By Tracy Burger

Age: Any Age

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: NSAIDs, Acetaminophen

Disqualifiers: Chronic kidney disease, Opioid abuse, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing whether using common painkillers like ibuprofen after childbirth is safe for women who had severe high blood pressure during pregnancy. The study aims to see if these painkillers make their condition worse. Researchers hope to find out if these drugs can be safely used to reduce the need for stronger pain medications like opioids. Ibuprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) commonly prescribed for pain relief and inflammation.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have been using antihypertensive medications before 20 weeks of pregnancy, you cannot participate in the trial.

Is it safe to use NSAIDs for preeclampsia?

Research suggests that NSAIDs like naproxen may help reduce kidney damage in preeclampsia, but they can also be associated with postpartum high blood pressure in women with severe preeclampsia. Low-dose aspirin is considered safe and can lower the risk of preeclampsia during pregnancy. ^{1 2 3 4 5}

How does the drug Oxycodone differ from other treatments for preeclampsia?

The research provided does not contain relevant information about Oxycodone as a treatment for preeclampsia, as it primarily focuses on NSAIDs and other drugs like pravastatin and metformin for this condition. ^{2 3 4 5 6}

Eligibility Criteria

This trial is for women over 23 weeks pregnant at Barnes-Jewish Hospital diagnosed with severe preeclampsia, which includes very high blood pressure or issues like low platelets, liver problems, kidney trouble, lung fluid build-up, or persistent headaches. It's not for those who can't consent, have peptic ulcers or allergies to pain relievers used in the study, took certain blood pressure drugs early in pregnancy, have chronic kidney disease or a history of opioid abuse.

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

You have a stomach ulcer.

You are allergic to acetaminophen.

You are allergic to NSAIDs.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either an NSAID-free analgesic bundle or an NSAID analgesic bundle postpartum

Up to 7 days

Daily monitoring during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment, including opioid use, blood pressure, and antihypertensive requirements

6 weeks

Regular follow-up visits

Treatment Details

Interventions

• Acetaminophen (Analgesic)
• Ibuprofen (Nonsteroidal Anti-inflammatory Drug)
• Ketorolac (Nonsteroidal Anti-inflammatory Drug)
• Oxycodone (Opioid Analgesic)

Trial Overview The study tests if adding nonsteroidal anti-inflammatory drugs (like Ibuprofen and Ketorolac) to standard pain relief methods after childbirth is just as good at managing high blood pressure as the usual treatment alone. Women will be randomly assigned to receive either the new combination of medications or the standard care.

Participant Groups

Group I: NSAID Analgesic bundle Experimental Treatment 4 Interventions

Ibuprofen 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

Group II: NSAID free analgesic bundle Active Control 2 Interventions

Acetaminophen 1000mg q 8 hrs as needed for pain, and Oxycodone 5 to 10 mg q 4 hrs as needed for pain.

Oxycodone is already approved in Canada for the following indications:

Approved in Canada as OxyContin for:

• Moderate to severe pain

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

Daily low-dose aspirin taken during pregnancy is effective in reducing the risk of preeclampsia, a serious condition that can affect both the mother and baby.

The use of low-dose aspirin is considered safe for pregnant individuals, making it a beneficial intervention to prevent adverse pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Another good reason to recommend low-dose aspirin. Oyola, S., Kirley, K.[2018]

In a study using a preeclampsia model, naproxen was found to be more effective than celecoxib and diclofenac in reducing renal damage and improving kidney function in pregnant dams, suggesting it may be a safer option for managing pain during pregnancy.

Naproxen significantly decreased markers of oxidative stress and inflammation in the kidneys, indicating its potential to mitigate the harmful effects of preeclampsia on renal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The suppression of MAPK/NOX/MMP signaling prompts renoprotection conferred by prenatal naproxen in weaning preeclamptic rats. Abdelhady, SA., Ali, MA., Yacout, DM., et al.[2023]

In a study involving pregnant rats, naproxen was found to be the most effective NSAID in reducing cardiovascular damage associated with preeclampsia, as it significantly decreased cardiac damage markers and improved heart health compared to celecoxib and diclofenac.

While all NSAIDs reduced inflammatory and antiangiogenic factors related to preeclampsia, naproxen uniquely minimized increases in cardiac size and specific biochemical markers, suggesting it may offer better protection against the cardiovascular effects of preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gestational NSAIDs distinctly reprogram cardiac injury in preeclamptic rats: Roles of cyclooxygenase, apoptotic and autophagic trails. Ali, MA., Abdelhady, SA., Yacout, DM., et al.[2022]

In a study of 399 women with severe preeclampsia, the use of NSAIDs (like ibuprofen or ketorolac) did not lead to higher rates of persistent postpartum hypertension compared to those who did not use NSAIDs, with similar blood pressure outcomes observed.

The study also found no significant differences in severe maternal complications, such as pulmonary edema or renal dysfunction, between women who received NSAIDs and those who did not, suggesting that NSAIDs can be safely used in this population without increasing the risk of these adverse outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features. Viteri, OA., England, JA., Alrais, MA., et al.[2021]

Pravastatin has emerged as a promising candidate for preventing preeclampsia, showing beneficial effects in preclinical studies and early clinical trials, with several large prevention trials currently underway to confirm its efficacy.

Other potential treatments, including proton-pump inhibitors, metformin, and natural compounds, are also being evaluated for their ability to target the underlying mechanisms of preeclampsia, indicating a broad interest in repurposing existing drugs and exploring new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. Tong, S., Kaitu'u-Lino, TJ., Hastie, R., et al.[2022]

Rofecoxib, a selective COX-2 inhibitor, was associated with a significantly higher rate of hospitalizations due to acute hypertension compared to celecoxib, with a 3.8-fold increase in reporting rates during the first three years of marketing.

The findings align with previous clinical trial data, indicating that rofecoxib may pose a greater risk for hypertension, particularly in older patients who are already at higher risk for cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin. Brinker, A., Goldkind, L., Bonnel, R., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Another good reason to recommend low-dose aspirin. [2018]

2. England pubmed.ncbi.nlm.nih.gov

The suppression of MAPK/NOX/MMP signaling prompts renoprotection conferred by prenatal naproxen in weaning preeclamptic rats. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Gestational NSAIDs distinctly reprogram cardiac injury in preeclamptic rats: Roles of cyclooxygenase, apoptotic and autophagic trails. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin. [2018]