310 Participants Needed

Acetaminophen + Ibuprofen for Patent Ductus Arteriosus

Recruiting at 8 trial locations
LT
Overseen ByLaura Thomas, MSc
Age: < 18
Sex: Any
Trial Phase: Phase 2
Sponsor: Mount Sinai Hospital, Canada
Must be taking: Ibuprofen
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 7 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new combination of ibuprofen and IV acetaminophen to treat a heart problem in very premature babies. These babies often don't respond well to just one drug, so using two drugs together might work better. The goal is to see if this combination is safer and more effective than using ibuprofen alone. Ibuprofen is commonly used to close the ductus arteriosus in premature newborns, and IV acetaminophen has shown effectiveness in similar treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. It is best to discuss this with the trial team or your doctor.

Is the combination of acetaminophen and ibuprofen generally safe for humans?

Ibuprofen, when taken at higher doses, has similar vascular risks to coxibs (a type of painkiller), but no specific safety data for the combination of acetaminophen and ibuprofen in humans is provided in the available research.12345

How does the drug combination of acetaminophen and ibuprofen differ from other treatments for patent ductus arteriosus?

The combination of acetaminophen (paracetamol) and ibuprofen for treating patent ductus arteriosus (PDA) in preterm infants is unique because it aims to improve the closure rate of the ductus arteriosus compared to using ibuprofen alone. While ibuprofen is already effective for PDA, adding acetaminophen may enhance its effectiveness, offering a potentially better treatment option for this condition.678910

What data supports the effectiveness of the drug combination of acetaminophen and ibuprofen for treating patent ductus arteriosus?

Research shows that ibuprofen is as effective as indomethacin in closing patent ductus arteriosus in preterm infants, with fewer side effects. This suggests that ibuprofen, a component of the drug combination, is effective for this condition.6781112

Who Is on the Research Team?

AJ

Amish Jain, MD PhD

Principal Investigator

MOUNT SINAI HOSPITAL

Are You a Good Fit for This Trial?

This trial is for extremely premature infants (born before 27 weeks) with a heart condition called PDA, where the duct fails to close after birth. Infants must not have had previous PDA treatment, except for indomethacin used to prevent bleeding in the brain. They should also have normal kidney and liver function and an adequate platelet count.

Inclusion Criteria

My baby was born before 27 weeks of pregnancy.
Permission given by the attending clinician to approach and then consent obtained from parents
I am set to start treatment with ibuprofen through IV or feeding tube.
See 1 more

Exclusion Criteria

Your liver is not working well, as shown by high levels of a liver enzyme called ALT.
Your platelet count is less than 50,000 per drop of blood.
I have been treated for PDA with drugs, except for indomethacin used to prevent brain bleeding.
See 4 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either combination therapy with ibuprofen and acetaminophen or standard monotherapy with ibuprofen for PDA treatment

3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including respiratory support, NEC, mortality, and BPD severity

Up to 250 days

Outcome Assessment

Assessment of PDA treatment success and other secondary outcomes

6-10 days post treatment initiation

What Are the Treatments Tested in This Trial?

Interventions

  • Acetaminophen Injection
  • Ibuprofen
Trial Overview The study tests if giving Ibuprofen together with IV Acetaminophen is more effective than Ibuprofen alone for treating PDA in very early-born babies. The goal is to see if this combination can improve outcomes by acting on different pathways that keep the duct open.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Combination TherapyExperimental Treatment2 Interventions
Group II: Standard Clinical Practice - MonotherapyPlacebo Group2 Interventions

Ibuprofen is already approved in United States, Canada, European Union, Japan, China, Switzerland for the following indications:

🇺🇸
Approved in United States as Advil for:
🇨🇦
Approved in Canada as Motrin for:
🇪🇺
Approved in European Union as Nurofen for:
🇯🇵
Approved in Japan as Ibuprofen for:
🇨🇳
Approved in China as Ibuprofen for:
🇨🇭
Approved in Switzerland as Ibuprofen for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Mount Sinai Hospital, Canada

Lead Sponsor

Trials
210
Recruited
70,700+

John Hunter Hospital

Collaborator

Trials
8
Recruited
1,700+

Royal Alexandra Hospital

Collaborator

Trials
20
Recruited
9,300+

Centre Hospitalier de l'Universite Laval (CHUL)

Collaborator

Trials
3
Recruited
780+

Royal North Shore Hospital

Collaborator

Trials
42
Recruited
7,900+

Prince of Wales Hospital, Shatin, Hong Kong

Collaborator

Trials
55
Recruited
21,700+

Sunnybrook Health Sciences Centre

Collaborator

Trials
693
Recruited
1,569,000+

McMaster Children's Hospital

Collaborator

Trials
43
Recruited
19,900+

The Rotunda Hospital

Collaborator

Trials
12
Recruited
4,300+

Published Research Related to This Trial

Ibuprofen (IBU) was found to be as effective as indomethacin (IND) in closing patent ductus arteriosus (PDA) in extremely low-birthweight infants, with no significant differences in closure rates or the need for surgical ligation between the two treatments.
IBU demonstrated a better safety profile regarding short-term renal function, as indicated by higher urine volume and lower levels of urinary L-type fatty acid binding protein compared to IND, suggesting less renal impairment in infants treated with IBU.
The influence on renal function of ibuprofen treatment for patent ductus arteriosus in extremely low birthweight infants.Nishizaki, N., Matsuda, A., Yoneyama, T., et al.[2020]
A meta-analysis of nine trials involving 566 preterm infants found that ibuprofen (IBU) and indomethacin (INDO) are equally effective in closing patent ductus arteriosus (PDA), with no significant difference in efficacy (P = 0.70).
However, ibuprofen was associated with significantly lower increases in serum creatinine levels and higher urine output compared to indomethacin, indicating better renal safety and less adverse effects on organ blood flow.
A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus.Thomas, RL., Parker, GC., Van Overmeire, B., et al.[2018]
Current ibuprofen dosing regimens for treating patent ductus arteriosus (PDA) may be inadequate, and simulations suggest that a new regimen could improve efficacy and safety.
The proposed regimen starts with an initial dose of 18 mg/kg followed by 4 mg/kg every 12 hours, which maintains effective drug levels while reducing peak concentrations, and should be adjusted to 5 mg/kg every 12 hours after 96 hours of postnatal age.
Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns.Flint, RB., Ter Heine, R., Spaans, E., et al.[2019]

Citations

The influence on renal function of ibuprofen treatment for patent ductus arteriosus in extremely low birthweight infants. [2020]
A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus. [2018]
Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns. [2019]
Dose-finding study of ibuprofen in patent ductus arteriosus using the continual reassessment method. [2022]
Is ibuprofen superior to indomethacin for patent ductus arteriosus in Japanese preterm infants? [2021]
[Pharmacovigilance update]. [2016]
[Pharmacovigilance and teratovigilance]. [2013]
An algorithm to detect adverse drug reactions in the neonatal intensive care unit. [2021]
Epidemiology of adverse drug reactions in the newborn. [2006]
10.United Statespubmed.ncbi.nlm.nih.gov
Improving Recognition and Reporting of Adverse Drug Reactions in the NICU: A Quality Improvement Project. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Adding Paracetamol to Ibuprofen for the Treatment of Patent Ductus Arteriosus in Preterm Infants: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. [2019]
12.United Statespubmed.ncbi.nlm.nih.gov
Oral ibuprofen is superior to oral paracetamol for patent ductus arteriosus in very low and extremely low birth weight infants. [2022]
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