Inhaled Nitric Oxide for ARDS-related Pulmonary Hypertension

Overseen By Emine Gholian

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yuri Matusov

Disqualifiers: Cardiogenic shock, Pulmonary hypertension, Valvular disease, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests inhaled nitric oxide (iNO) to determine its effectiveness for people with ARDS, a serious lung condition, who develop high blood pressure in their lungs. Researchers aim to discover if early administration of iNO can improve heart and lung function. The trial targets individuals with ARDS who are on a breathing machine. Those with other heart problems or pre-existing high blood pressure in the lungs may not qualify. As an Early Phase 1 trial, this research seeks to understand how iNO works in people, offering participants the chance to be among the first to receive this potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that inhaled nitric oxide is likely to be safe for humans?

Research has shown that inhaled nitric oxide (iNO) is generally safe for both children and adults. In a real-world study, only a small number of patients experienced side effects—1.0% in children and 1.2% in adults. This indicates that most people do not encounter serious side effects from iNO.

iNO is often used as an emergency treatment for adults with severe breathing problems, suggesting its safety even in critical situations. Although this trial is in the early stages and there is limited safety data specifically for ARDS-related lung issues, the existing real-world data provides some reassurance about the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Inhaled Nitric Oxide is unique because it offers a new way to tackle ARDS-related pulmonary hypertension by directly targeting the lungs with a gas that can relax and widen blood vessels. Unlike traditional treatments, which often involve systemic medications, this approach allows for localized treatment, potentially reducing side effects. Researchers are excited about this treatment because it can quickly improve oxygenation and reduce the strain on the heart, offering a more immediate response compared to conventional therapies.

What evidence suggests that inhaled nitric oxide might be an effective treatment for ARDS-related pulmonary hypertension?

Research has shown that inhaled nitric oxide (iNO), which participants in this trial may receive, can help people with acute respiratory distress syndrome (ARDS) breathe better. Studies have found that iNO can increase oxygen levels and lower high blood pressure in the lungs, a common issue in ARDS. Evidence also suggests that iNO might help prevent lung inflammation and blood clots, particularly in COVID-19 cases. These effects indicate that iNO could improve the function of other organs by enhancing blood flow in the lungs. Although more research is needed, these findings provide a promising basis for using iNO to treat ARDS-related lung issues. ^{1 3 5 6 7}

Who Is on the Research Team?

Yuri Matusov, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with ARDS who are starting to show signs of high blood pressure in the lungs. It's open to those who haven't yet received treatment for this specific complication.

Inclusion Criteria

Diagnosis of ARDS based on the Berlin criteria

I am on a mechanical ventilator.

Exclusion Criteria

Consent cannot be obtained from the patient or his/her surrogates

Refusal of consent

Opinion of treating physicians that enrolling the patient in the study would be detrimental to his/her outcome

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive inhaled nitric oxide (iNO) for ARDS-related pulmonary hypertension

4 days

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Nitric Oxide

Trial Overview The study tests if inhaling nitric oxide (iNO) early on can help manage increased lung blood pressure and improve overall health in ARDS patients.

How Is the Trial Designed?

Group I: iNOMAX Experimental Treatment 1 Intervention

Inhaled Nitric Oxide is already approved in United States, European Union for the following indications:

Approved in United States as INOmax for:

• Hypoxic respiratory failure
• Pulmonary hypertension

Approved in United States as Genosyl for:

• Hypoxic respiratory failure
• Pulmonary hypertension

Approved in European Union as INOmax for:

• Persistent pulmonary hypertension of the newborn
• Acute hypoxic respiratory failure

Who Is Running the Clinical Trial?

Yuri Matusov

Lead Sponsor

Trials

1

Recruited

20+

Mallinckrodt

Industry Sponsor

Trials

202

Recruited

15,700+

Mario Saltarelli

Mallinckrodt

Chief Medical Officer

MD

Siggi Olafsson

Mallinckrodt

Chief Executive Officer

PhD in Pharmacy

Published Research Related to This Trial

Inhaled nitric oxide (iNO) can be safely managed by trained nurses during the transport of critically ill patients, as demonstrated by a study involving patients transported from March 2020 to August 2022.

Out of the patients studied, only 16.7% experienced hypotension, which was manageable and resolved with medication adjustments, while no serious adverse events like worsening hypoxemia or cardiac arrest were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Nurse-Managed Inhaled Nitric Oxide During Critical Care Interfacility Transport. Troncoso, R., Garfinkel, EM., Kaul, K., et al.[2023]

Inhaled nitric oxide (iNO) therapy significantly increases the risk of renal dysfunction in patients with acute respiratory distress syndrome (ARDS), with an adjusted hazard ratio of 1.59 after accounting for confounding factors.

Older patients (aged 65 and above) are particularly vulnerable to kidney injury associated with iNO therapy, highlighting the need for careful monitoring in this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: a propensity-matched cohort study. Ruan, SY., Wu, HY., Lin, HH., et al.[2022]

The implementation of clinical guidelines for inhaled nitric oxide (iNO) therapy in a pediatric intensive care unit led to a significant reduction in the duration of iNO treatment, from a median of 162 hours to 76 hours, without compromising patient care.

Following the guidelines, there was a notable cost savings of $4,600 per patient, demonstrating that standardized protocols can enhance efficiency and reduce unnecessary expenses in iNO therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Quality Improvement Initiative to Standardize Use of Inhaled Nitric Oxide in the PICU. Karsies, TJ., Evans, L., Frost, R., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06249633

Inhaled Nitric Oxide for ARDS-related Pulmonary ... Open-label pilot study of early inhaled nitric oxide (iNO) for patients developing de novo pulmonary hypertension during Acute Respiratory Distress Syndrome ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10402704/

Inhaled Nitric Oxide in Acute Respiratory Distress ... In addition, iNO may act as a viricidal agent and prevent lung hyperinflammation and thrombosis of the pulmonary vasculature in the specific setting of COVID-19 ...

3. withpower.com withpower.com/trial/early-phase-1-respiratory-distress-syndrome-1-2024-1d608

Inhaled Nitric Oxide for ARDS-related Pulmonary ... Open-label pilot study of early inhaled nitric oxide (iNO) for patients developing de novo pulmonary hypertension during Acute Respiratory Distress Syndrome ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1130634323002568

Inhaled nitric oxide in adult patients with acute respiratory ... Inhaled nitric oxide variably improves oxygenation and pulmonary hypertension in patients with acute respiratory distress syndrome. J Trauma., 39 (3) (1995) ...

5. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/00000486

Inhaled Nitric Oxide for ARDS-Related Pulmonary Hypertension Researchers want to learn whether the use of inhaled nitric oxide can improve pulmonary hypertension and thus improve the ability of other organs to work better ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11018662/

Real-world safety and effectiveness of inhaled nitric oxide ... INOflo was generally well tolerated; 15 and 20 adverse drug reactions were reported in 14 pediatrics (1.0%) and 18 adults (1.2%), respectively.

7. trial.medpath.com trial.medpath.com/clinical-trial/93755573e6f7becc/nct06249633-pilot-study-inhaled-nitric-oxide-ards-pulmonary-hypertension

Inhaled Nitric Oxide for ARDS-related Pulmonary Hypertension The study aims to determine whether iNO has possible hemodynamic and clinical benefits when given early in the course of ARDS to patients with evidence of ...