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.
12345Eligibility 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.
+4 more
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: NSAID Analgesic bundleExperimental Treatment4 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 bundleActive Control2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Barnes Jewish HospitalSaint Louis, MO
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
References
Another good reason to recommend low-dose aspirin. [2018]Evidence shows that daily low-dose aspirin during pregnancy can safely lower the risk of preeclampsia and other adverse outcomes.
The suppression of MAPK/NOX/MMP signaling prompts renoprotection conferred by prenatal naproxen in weaning preeclamptic rats. [2023]Although nonsteroidal antiinflammatory drugs (NSAIDs) are frequently used for fever and pain during pregnancy, their possible interaction with perinatal renal injury induced by preeclampsia (PE) has not been addressed. Here, studies were undertaken in the N(gamma)-nitro-L-arginine methyl ester (L-NAME) PE model to assess the influence of gestational NSAIDs on renal damage in weaning dams. PE-evoked increments and decrements in urine protein and creatinine clearance, respectively, were intensified by celecoxib and weakened by diclofenac or naproxen. Naproxen also improved renal cloudy swelling, necrosis, and reduced glomerular area evoked by PE. The concomitant rises in renal expression of markers of oxidative stress (NOX2/4), extracellular matrix metaloproteinase deposition (MMP9), and prostanoids (PGE2, PGF2α, TXA2) were all more effectively reduced by naproxen compared with celecoxib or diclofenac. Western blotting showed tripled expression of mitogen-activated protein kinases (MAPKs; p-p38, p-JNK1, p-ERK1, p-ERK2) in PE kidneys that was overturned by all NSAIDs, with naproxen producing the largest drop in p-ERK2 expression. The PE-provoked elevation in renal expression of autophagic marker LC3 was reduced by naproxen and diclofenac, but not celecoxib. The data suggests superior effect for naproxen over other NSAIDs in rectifying preeclamptic renal injury and predisposing inflammatory, oxidative, autophagic, and fibrotic signals.
Gestational NSAIDs distinctly reprogram cardiac injury in preeclamptic rats: Roles of cyclooxygenase, apoptotic and autophagic trails. [2022]Considering the role of cyclooxygenases (COX) in placental programming induced by preeclampsia (PE), we investigated whether gestational exposure to nonsteroidal antiinflammatory drugs (NSAIDs) with different COX-1/2 selectivity would variably modulate pre- and postnatal (weaning time, i.e. 3 weeks after delivery) cardiovascular manifestations of PE.
Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features. [2021]To estimate whether nonsteroidal antiinflammatory drugs (NSAIDs) are associated with persistent postpartum hypertension in a cohort of women with preeclampsia and severe features.
Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. [2022]There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.
Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin. [2018]Data on file with the US FDA, and other published studies, suggest that the selective cyclo-oxygenase (COX)-2 inhibitor NSAID rofecoxib has a greater hypertensive adverse effect than other NSAIDs, including celecoxib. In this study we describe a pharmacoepidemiologic analysis of spontaneous adverse event reports of acute, clinically serious hypertension (as defined by hospitalisation) reported in association with rofecoxib, celecoxib, nabumetone and oxaprozin. The objective of this analysis is to assess whether postmarketing data are consistent with results of clinical trials. We also collapse cases into series for the identification of possible risk factors for clinically severe, NSAID-associated hypertension.