Inhaled Nitric Oxide in Severe Obesity

NCT06675435 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: 2024p003089
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn about the effects of inhaled nitric oxide on oxygenation and lung perfusion in participants with severe obesity who have acute hypoxemic respiratory failure and are on mechanical ventilation The main questions it aims to answer are:

1. 1.In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on oxygenation in participants with severe obesity compared to participants with normal body weight.
2. 2.In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on lung perfusion and heart function in participants with severe obesity compared to participants with normal body weight.
3. 3.In acute hypoxemic respiratory failure, does severe obesity impact nitric oxide signaling pathways?

Conditions

Obesity; Respiratory Insufficiency; Hypoxemic Respiratory Failure; Nitric Oxide

Keywords

severe obesity; acute hypoxemic respiratory failure; intrapulmonary shunt; inhaled nitric oxide

Outcome Measures

Primary Outcomes (1)

• Intrapulmonary shunt

  Intrapulmonary shunt will be defined as the difference in intrapulmonary shunt (%) to inhaled nitric oxide. Intrapulmonary shunt will be defined using the modified Berggren equation based on central venous and arterial oxygen concentrations from a central venous and peripheral arterial catheter.

  Intrapulmonary shunt will be assessed before inhaled nitric oxide, at 15 minutes after inhaled nitric oxide, and at 15 minutes after inhaled nitric oxide discontinuation.

Secondary Outcomes (3)

• Regional pulmonary perfusion

  Regional pulmonary perfusion will be assessed before inhaled nitric oxide, at 15 minutes after inhaled nitric oxide, and at 15 minutes after inhaled nitric oxide discontinuation.

• Gas exchange

  Gas exchange will be assessed before inhaled nitric oxide, at 15 minutes after inhaled nitric oxide, and at 15 minutes after inhaled nitric oxide discontinuation.

• Right ventricular systolic pressure

  Right ventricular systolic pressure will be assessed before inhaled nitric oxide, at 15 minutes after inhaled nitric oxide, and at 15 minutes after inhaled nitric oxide discontinuation.

Other Outcomes (2)

• Nitric oxide activity

  Nitric oxide activity will be assessed before inhaled nitric oxide, at 15 minutes after inhaled nitric oxide, and at 15 minutes after inhaled nitric oxide discontinuation. Nitric oxide activity will be measured in control participants (single timepoint).

• Nitric oxide signaling pathways

  Biomarkers will be measured after enrollment in participants with and without acute hypoxemic respiratory failure (single time point)

Study Arms (2)

Acute hypoxemic respiratory failure

EXPERIMENTAL

Participants (n = 40) with acute hypoxemic respiratory failure will receive inhaled nitric oxide (20 ppm) for 15 min.

Device: Nitric oxide

Participants without acute hypoxemic respiratory failure

NO INTERVENTION

Participants (n = 20) without acute hypoxemic respiratory failure will not receive inhaled nitric oxide

Interventions

Nitric oxide DEVICE

20ppm for 15 minutes delivered by INO max(Nitric Oxide) Company : INO therapeutics, Inc.

Acute hypoxemic respiratory failure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute hypoxemic respiratory failure, defined as persistent hypoxemia (PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 315) and on invasive mechanical ventilation for \< 72 hours
• Presence of an arterial and central venous catheter (for blood gas measurement)
• Admitted to a participating MGH ICU

You may not qualify if:

• Age \< 18 years
• Pregnancy or known active breastfeeding
• Prisoner or Incarceration
• Inability or unwillingness of subject or legal surrogate/representative to give written informed consent
• Use of inhaled or oral pulmonary vasodilatory therapy within the 24 hours preceding study enrollment
• Contraindication to inhaled NO
• Baseline Methemoglobin ≥ 3%
• Known left ventricle ejection fraction \< 20%
• Known history of G6PD deficiency or cytochrome issues
• Prior adverse reaction to inhaled nitric oxide
• Presence of pneumothorax or acute pulmonary embolism
• Chronic hypoxemia requiring home supplemental non-invasive oxygen (nasal cannula or positive pressure ventilation) or home mechanical ventilation
• Chronic pulmonary vascular disease on home chemical vasodilator support (e.g., sildenafil)
• History of lung resection or transplant
• Hemodynamic instability at the time of potential study enrollment defined as:

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• Spina S, Marrazzo F, Morais CCA, Victor M, Forlini C, Guarnieri M, Bastia L, Giudici R, Bassi G, Xin Y, Cereda M, Amato M, Langer T, Berra L, Fumagalli R. Modulation of pulmonary blood flow in patients with acute respiratory failure. Nitric Oxide. 2023 Jul 1;136-137:1-7. doi: 10.1016/j.niox.2023.05.001. Epub 2023 May 10.

  PMID: 37172929 BACKGROUND

• Borges JB, Suarez-Sipmann F, Bohm SH, Tusman G, Melo A, Maripuu E, Sandstrom M, Park M, Costa EL, Hedenstierna G, Amato M. Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse. J Appl Physiol (1985). 2012 Jan;112(1):225-36. doi: 10.1152/japplphysiol.01090.2010. Epub 2011 Sep 29.

  PMID: 21960654 BACKGROUND

MeSH Terms

Conditions

Obesity; Respiratory Insufficiency; Obesity, Morbid

Interventions

Fractional Exhaled Nitric Oxide Testing

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Breath Tests; Diagnostic Techniques and Procedures; Diagnosis

Central Study Contacts

Timothy Gaulton, MD, MSc

CONTACT

6177263030; tgaulton@mgh.harvard.edu

Maurizio Cereda, MD

CONTACT

6177263030; mcereda@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anaesthesia

Model Details: In a prospective single center clinical study, participants with acute hypoxemic respiratory failure will receive inhaled nitric oxide for 15 minutes. Study outcomes will compare cardiopulmonary responses to inhaled nitric oxide (vs. no inhaled nitric oxide).

Study Record Dates

• First Submitted: November 4, 2024
• First Posted: November 5, 2024
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research.

Locations

US (1)