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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Inhaled Nitric Oxide for ARDS-related Pulmonary Hypertension?

Inhaled Nitric Oxide (iNO) is shown to improve oxygen levels and reduce high blood pressure in the lungs for patients with ARDS, especially those with severe breathing difficulties. It helps by directing blood flow to better-ventilated areas of the lungs, which can improve breathing without major side effects. ^{1 2 3 4 5}

Is inhaled nitric oxide generally safe for humans?

Inhaled nitric oxide (iNO) is generally considered safe with limited side effects, though it may cause low blood pressure in some cases. Studies have shown that it can be safely managed by trained healthcare professionals, and while there are concerns about potential kidney issues, more research is needed to fully understand these risks. ^{4 6 7 8 9}

How does the drug inhaled nitric oxide differ from other treatments for ARDS-related pulmonary hypertension?

Inhaled nitric oxide is unique because it directly targets the lungs by dilating blood vessels in ventilated areas, improving oxygen levels without affecting the rest of the body. This makes it different from other treatments that may not be as selective or may have more systemic effects. ^{2 3 4 10 11}

What is the purpose of this trial?

Open-label pilot study of early inhaled nitric oxide (iNO) for patients developing de novo pulmonary hypertension during Acute Respiratory Distress Syndrome (ARDS.) 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 elevated pulmonary artery pressure.

Research Team

Yuri Matusov, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

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

I have been diagnosed with a severe heart condition that affects its ability to pump blood.

I have a serious heart valve condition.

I have a heart condition affecting my heart's muscle.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Inhaled nitric oxide for rescue treatment of refractory hypoxemia in ARDS patients]. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide therapy in adults: European expert recommendations. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Our paper 20 years later: Inhaled nitric oxide for the acute respiratory distress syndrome--discovery, current understanding, and focussed targets of future applications. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Safety of Nurse-Managed Inhaled Nitric Oxide During Critical Care Interfacility Transport. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

A Stewardship Program to Optimize the Use of Inhaled Nitric Oxide in Pediatric Critical Care. [2019]

6. England 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

A Quality Improvement Initiative to Standardize Use of Inhaled Nitric Oxide in the PICU. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Nitric oxide: Clinical applications in critically ill patients. [2023]

10. Spain pubmed.ncbi.nlm.nih.gov

[Utility of inhaled nitric oxide in patient with acute respiratory distress syndrome and un-operated Fallot's tetralogy]. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Long-term inhaled nitric oxide plus phosphodiesterase 5 inhibitors for severe pulmonary hypertension. [2013]