Clinical trial NCT06675435: Inhaled Nitric Oxide in Severe Obesity
Official title: The Effect of Inhaled Nitric Oxide on Intrapulmonary Shunt in Acutely Hypoxemic Patients With Severe Obesity
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Obesity
Respiratory Insufficiency
Hypoxemic Respiratory Failure
Nitric Oxide
Keywords: severe obesity
acute hypoxemic respiratory failure
intrapulmonary shunt
inhaled nitric oxide
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2024-11-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: DIAGNOSTIC

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. 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. 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. In acute hypoxemic respiratory failure, does severe obesity impact nitric oxide signaling pathways?

Participants with acute hypoxemic respiratory failure will be exposed to inhaled nitric oxide (20 ppm) while being clinically monitored.

Detailed description: The study is a single-center, open-label clinical trial in mechanically ventilated participants with acute hypoxemic respiratory failure. The primary aim is to assess changes in intrapulmonary shunt (primary study outcome) to inhaled nitric oxide in participants with severe obesity and those with normal body weight. The secondary aims are to determine differences in regional lung perfusion (measured by electrical impedance tomography), right ventricular pressure (measured by transthoracic echocardiography), and biomarkers of nitric oxide signaling dysfunction (nitric oxide activity, pro-inflammatory cytokines, endothelial glycocalyx fragments)

The primary study intervention involves inhaled nitric oxide at 20 ppm for 15 minutes. The investigators will compare inhaled nitric oxide response in participants with severe obesity (defined by body mass index greater than or equal to 40) to participants with normal body weight (defined by body mass index 18.5-24.9). 40 participants with acute hypoxemic respiratory failure will be enrolled (20 with severe obesity and 20 with normal body weight). The investigators will enroll a separate cohort of mechanically ventilated participants who do not have acute hypoxemic respiratory failure (10 with severe obesity and 10 with normal body weight). In this cohort, investigators will collect additional blood at a single time point to compare levels of nitric oxide signaling pathways between patients with and without acute hypoxemia across body weight.

Eligibility criteria: For participants with acute hypoxemic respiratory failure

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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:

  * Persistent systolic blood pressure \< 90 mmHg or \>180 mmHg despite the use of vasopressor or vasodilators or
  * Requiring an increment in inotropic-vasopressors over the past two hours just before enrollment: more than 15 mcg/min for norepinephrine and dopamine, more than 10 mcg/min in epinephrine; and more than 50 mcg/ min for phenylephrine.

EIT assessments of lung perfusion will only be performed in participants who are already receiving neuromuscular blocking agents (e.g., cisatracurium) at the time of study enrollment. EIT assessments of lung perfusion will not be performed in participants who have the following contraindications to EIT perfusion monitoring:

* Hypernatremia (serum sodium \> 150 mEq/L)
* Usage of any devices with electric current generation such as pacemaker or internal cardiac defibrillator

For controls without acute hypoxemic respiratory failure

Inclusion Criteria:

* Receiving invasive mechanical ventilation and do not have a diagnosis of acute hypoxemic respiratory failure (PaO2/FiO2 \> 300 mmHg or SpO2/FiO2\> 315)
* Presence of an arterial catheter
* Admitted to a participating MGH ICU

Exclusion Criteria:

* 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

Primary outcomes:
measure: Intrapulmonary shunt
timeFrame: 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:
measure: Regional pulmonary perfusion
timeFrame: 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.
measure: Gas exchange
timeFrame: 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.
measure: Right ventricular systolic pressure
timeFrame: 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:
measure: Nitric oxide activity
timeFrame: 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).
measure: Nitric oxide signaling pathways
timeFrame: Biomarkers will be measured after enrollment in participants with and without acute hypoxemic respiratory failure (single time point)
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References:
citation: 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.
citation: 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.