40 Participants Needed

Nitric Oxide for Congenital Heart Disease

DS
Overseen ByDavid S Cooepr, MD
Age: < 18
Sex: Any
Trial Phase: Phase 3
Sponsor: Children's Hospital Medical Center, Cincinnati
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have recently been treated with steroids or are using inhaled nitric oxide (iNO) before surgery.

What evidence supports the effectiveness of the drug nitric oxide for congenital heart disease?

Inhaled nitric oxide is shown to be beneficial as a selective pulmonary vasodilator (a drug that widens blood vessels in the lungs) for treating pulmonary hypertension (high blood pressure in the lungs) in newborns with congenital heart disease, providing hemodynamic benefits (improvements in blood flow and pressure). However, these benefits have not been confirmed in randomized, placebo-controlled studies.12345

Is nitric oxide generally safe for use in humans?

Nitric oxide is involved in many body processes and has been studied for various conditions. It can cause side effects like headaches and low blood pressure due to its ability to widen blood vessels. However, it is generally considered safe when used appropriately, although targeting its effects to specific tissues remains a challenge.14567

How is the drug nitric oxide unique in treating congenital heart disease?

Nitric oxide is unique because it is inhaled and acts as a selective pulmonary vasodilator, meaning it specifically relaxes the blood vessels in the lungs, which can help manage pulmonary hypertension (high blood pressure in the lungs) in patients with congenital heart disease. This targeted action helps improve blood flow and oxygen delivery without affecting the rest of the body, unlike some other treatments.34589

What is the purpose of this trial?

Acute kidney injury (AKI) following cardiac surgery for congenital heart defects (CHD) in children affects up to 60% of high risk-patients and is a major cause of both short- and long-term morbidity and mortality. Despite effort, to date, no successful therapeutic agent has gained widespread success in preventing this postoperative decline in renal function. Nitric oxide is an intricate regulator of acute inflammation and coagulation and is a potent vasodilator. The investigators hypothesize that nitric oxide, administered during cardiopulmonary bypass (CPB), may reduce the incidence of AKI.

Eligibility Criteria

This trial is for newborns (up to 31 days old) who need heart surgery with cardiopulmonary bypass for congenital heart defects. They must weigh over 2 kg and be at least 36 weeks gestational age. Babies can't join if they've had a recent cardiac arrest, preoperative AKI, certain lung or kidney conditions, steroid treatments, or are on other trials.

Inclusion Criteria

My newborn is having heart surgery with CPB for congenital heart disease.

Exclusion Criteria

Non-English speakers
My kidney ultrasound showed structural abnormalities.
I need surgery urgently.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Nitric oxide is administered during cardiopulmonary bypass (CPB) to reduce the incidence of AKI

Intraoperative
1 visit (in-person, surgical procedure)

Follow-up

Participants are monitored for AKI and other outcomes postoperatively

72 hours
Continuous monitoring during hospital stay

Extended Follow-up

Participants are monitored for long-term kidney function and recovery

4 weeks

Treatment Details

Interventions

  • Nitric Oxide
Trial Overview The study tests whether nitric oxide given during heart surgery can lower the risk of acute kidney injury in newborns with congenital heart defects. It's exploring if this gas helps protect the kidneys by reducing inflammation and improving blood flow during surgery.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Nitric OxideExperimental Treatment1 Intervention
Intraoperative NO entrained at 20 ppm into the oxygenator of the CPB circuit with standard care
Group II: OxygenPlacebo Group1 Intervention
Standard CPB without NO administered at any point intraoperatively

Nitric Oxide is already approved in United States for the following indications:

๐Ÿ‡บ๐Ÿ‡ธ
Approved in United States as Inomax for:
  • Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension
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Approved in United States as Noxivent for:
  • Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension
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Approved in United States as GeNOsyl for:
  • Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials
844
Recruited
6,566,000+

Mallinckrodt

Industry Sponsor

Trials
202
Recruited
15,700+

Mario Saltarelli

Mallinckrodt

Chief Medical Officer

MD

Siggi Olafsson profile image

Siggi Olafsson

Mallinckrodt

Chief Executive Officer

PhD in Pharmacy

Indiana University

Collaborator

Trials
1,063
Recruited
1,182,000+

Findings from Research

Nitric oxide (NO) is identified as a key endothelium-derived relaxing factor (EDRF) that regulates smooth muscle tone and platelet behavior, with its release being significantly inhibited by N omega-Monomethylarginine (N-MeArg), suggesting its crucial role in vascular relaxation.
The study demonstrated that the relaxation effect induced by histamine and acetylcholine in the guinea pig pulmonary artery is dependent on EDRF, and that this effect can be reversed by L-arginine, indicating that EDRF likely originates from arginine metabolism in the endothelium.
Identification of arginine as a precursor of endothelium-derived relaxing factor.Sakuma, I., Stuehr, DJ., Gross, SS., et al.[2022]
Nitric oxide (NO) has a complex role in cardiac health, showing both cardioprotective effects during myocardial ischemia-reperfusion and potential to worsen reperfusion injury by producing harmful peroxynitrite.
Exogenous supplementation of NO, particularly through agents like protamine sulfate, may enhance NO production and provide therapeutic benefits in conditions like pulmonary hypertension and atherosclerotic coronary heart disease.
The role of nitric oxide in cardiac surgery.Nonami, Y.[2022]
Inhaled nitric oxide is an effective treatment for pulmonary hypertension in patients with congenital heart disease, particularly benefiting newborns, who made up 37% of the 400 patients treated at the center.
While it helps in diagnosing and managing conditions like total anomalous pulmonary venous connection and congenital mitral stenosis, the efficacy of inhaled nitric oxide has not been rigorously tested in randomized, placebo-controlled trials.
Inhaled nitric oxide in the neonate with cardiac disease.Atz, AM., Wessel, DL.[2022]

References

Identification of arginine as a precursor of endothelium-derived relaxing factor. [2022]
The role of nitric oxide in cardiac surgery. [2022]
Inhaled nitric oxide in the neonate with cardiac disease. [2022]
Endothelium-derived nitric oxide: actions and properties. [2022]
Endothelium-derived nitric oxide relaxes nonvascular smooth muscle. [2019]
Nitric oxide donor drugs: an update on pathophysiology and therapeutic potential. [2019]
Endothelium-derived nitric oxide: pharmacology and relationship to the actions of organic nitrate esters. [2019]
Inhaled nitric oxide in congenital heart disease. [2019]
Nitrates in different vascular beds, nitrate tolerance, and interactions with endothelial function. [2019]
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