NSAIDs for Preeclampsia

(PANDA Trial)

Recruiting at 1 trial location

Overseen By Tracy Burger

Age: Any Age

Sex: Female

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: NSAIDs, Acetaminophen

Disqualifiers: Chronic kidney disease, Opioid abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 7 days

286 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether adding nonsteroidal anti-inflammatory drugs (NSAIDs) to standard pain relief treatments affects the management of high blood pressure after childbirth in women with severe preeclampsia. It will compare two groups: one following a pain relief plan without NSAIDs and another with NSAIDs included. Women diagnosed with severe preeclampsia during pregnancy and delivering at Barnes-Jewish Hospital may be eligible. Those who have experienced high blood pressure or other severe symptoms related to preeclampsia might find this trial suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ibuprofen is generally safe for women with preeclampsia when used for pain relief after childbirth. Studies have found that ibuprofen does not increase the risk of severe high blood pressure compared to acetaminophen, indicating it is well-tolerated in this situation.

For ketorolac, another pain reliever in the trial, the safety information is more complex. Some studies suggest that ketorolac can be a safe non-opioid option after birth. However, concerns exist about using these drugs during pregnancy because they might cause kidney issues in newborns. Ketorolac is typically used after delivery, not during pregnancy, which may reduce these risks.

Overall, while ibuprofen and ketorolac are generally safe for pain relief after childbirth, some risks exist, especially with ketorolac. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores using NSAIDs, like ibuprofen and ketorolac, in managing pain for patients with preeclampsia, a condition typically treated with magnesium sulfate and antihypertensives. Unlike standard approaches that focus mainly on controlling blood pressure, the trial investigates how NSAIDs might offer effective pain relief while potentially minimizing opioid use, given their inclusion in both arm groups. This could provide a safer alternative for pain management during pregnancy, addressing concerns about opioid exposure for both mother and baby.

What evidence suggests that this trial's treatments could be effective for preeclampsia?

This trial will compare two analgesic bundles for women with preeclampsia. Research has shown that ibuprofen, part of the NSAID Analgesic bundle in this trial, and acetaminophen, included in both treatment arms, have similar effects on blood pressure in women with preeclampsia, a pregnancy condition characterized by high blood pressure. Studies indicate that ibuprofen does not prolong severe high blood pressure in these women. Ketorolac, which may replace ibuprofen in the NSAID Analgesic bundle, is also considered safe for women with severe preeclampsia and does not seem to affect blood pressure control after childbirth. Overall, pain relievers like ibuprofen and ketorolac do not appear to increase blood pressure after giving birth in women with preeclampsia. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Acetaminophen
• Ibuprofen
• Ketorolac
• Oxycodone

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as OxyContin for:

• Moderate to severe pain
• Chronic pain

Approved in European Union as OxyContin for:

• Severe pain
• Cancer pain

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9097787/

Effect of ibuprofen vs acetaminophen on postpartum ... The main finding of our study is that compared to acetaminophen, ibuprofen did not extend the duration of severe-range HTN in women with preeclampsia with ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2210778919304374

A randomized-controlled trial to assess the effect of ... In this randomized, controlled trial, we found that ibuprofen and acetaminophen were equivalent in effect or lack thereof on SBP postpartum after 24 h of drug ...

3. jogcr.com jogcr.com/article_697358.html

Determination and Comparison of the Effect of Ibuprofen ... ✓ The results revealed that in patients with preeclampsia, acetaminophen and ibuprofen to control postpartum pain have a similar impact on blood pressure.

4. ajog.org ajog.org/article/S0002-9378(25)00092-4/abstract

A randomized trial of postpartum ibuprofen in severe ... To evaluate the impact of ibuprofen on postpartum blood pressure outcomes in patients with hypertensive disorders of pregnancy with severe hypertension.

5. mdedge.com mdedge.com/obgyn/article/157725/obstetrics/ibuprofen-appears-safe-preeclampsia-study-says

Ibuprofen appears safe with preeclampsia, study says The study had a number of secondary outcomes, including time from delivery to last blood pressure reading of at least 150/100 mm Hg ...

6. ajog.org ajog.org/article/S0002-9378(18)30323-5/fulltext

Pain relief: determining the safety of ibuprofen with ... Key results from this well-designed and executed study show no difference in the duration of severe range blood pressures in the ibuprofen vs acetaminophen ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31586784/

A randomized-controlled trial to assess the effect of ... Conclusions: Among women with gestational hypertension and preeclampsia without severe features, ibuprofen is an equally safe option as ...