Vascular ARDS Recruitment After Inhaled Nitric Oxide

NCT05801224 | Suspended FDA Device

• 1 other identifier: 2023p000138
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Acute respiratory distress syndrome (ARDS) is when a person's lungs become inflamed, which can be caused by infection, trauma, surgery, blood transfusion, or burn. ARDS often leads to a situation where the person cannot breathe independently and needs machines' help. Once the lungs are inflamed, the small air sacs responsible for exchanging gases (i.e., ventilation) and the blood flow in the lungs (i.e., perfusion) can be affected. In the past, most research focused on studying ventilation physiology and how to help people breathe with machines. Less was done on perfusion because it requires imaging techniques such as computed tomography with intravenous contrast and radiation. One treatment option for low oxygen levels is inhaled nitric oxide (iNO), a gas that can dilate the lung blood vessels and improve oxygenation; however, it is not always clear whether this treatment will work. Electrical Impedance Tomography (EIT) is a bedside and accessible imaging technique that is radiation-free and non-invasive and can potentially detect changes in lung perfusion. EIT can perform multiple measurements; it is portable and accessible. This prospective interventional study aims to assess changes in regional blood perfusion in the lungs of patients with ARDS in response to iNO utilizing EIT. The main questions it aims to answer are:

1. 1.If EIT can measure lung regional perfusion response to an iNO challenge of 20ppm for 15 minutes.
2. 2.If EIT is comparable to dual-energy computed tomography (DECT), the gold-standard method to detect changes in regional lung perfusion.
3. 3.If EIT can be an imaging marker to identify ARDS severity
4. 4.Cohort 1 (n=60): Participants will be asked to be monitored by EIT before, during, and after the administration of iNO (20 ppm) for 15 minutes (OFF-ON-OFF)
5. 5.Cohort 2 (N=10): Participants will be asked to be monitored by EIT and DECT before and during the administration of iNO (20 ppm) for 15 minutes (OFF-ON).

Conditions

Acute Respiratory Distress Syndrome; Ventilation Perfusion Mismatch

Keywords

Acute respiratory distress syndrome; Ventilation/perfusion mismatch; Electrical impedance tomography; Inhaled nitric oxide; Dual-energy computed tomography

Outcome Measures

Primary Outcomes (1)

• Change in regional lung perfusion after the delivery of inhaled nitric oxide

  The primary outcome is to detect changes in regional perfusion distribution with the administration of inhaled nitric oxide with electrical impedance tomography by measuring changes in impedance.

  Day 1

Secondary Outcomes (1)

• Compare methods to detect change in regional lung perfusion after the delivery of inhaled nitric oxide

  Day 1

Other Outcomes (25)

• Age

  Day 1

• Gender

  Day 1

• Height

  Day 1

Study Arms (2)

Electrical Impedance Tomography

EXPERIMENTAL

A total of 60 subjects (cohort 1) will receive an inhaled nitric oxide (iNO) challenge (20 ppm) for 15 min. The investigators will measure ventilation and perfusion distributions using EIT before iNO ("OFF1"), after 15 min on iNO ("ON"), and after 15 min washout ("OFF2") to confirm baseline stability.

Device: Nitric Oxide

Electrical Impedance Tomography and Dual-Energy Computed Tomography

EXPERIMENTAL

In a subset of 10 subjects (cohort 2), EIT and DECT will be performed in a row at the same type of bed and body position. In cohort 2, the measurements will be before nitric oxide (iNO) and during iNO. The OFF-ON fashion for DECT imaging is to minimize the subject's exposure to radiation and reduce the time spent in the CT room.

Device: Nitric Oxide

Interventions

Nitric Oxide DEVICE

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

Also known as: inhaled nitric oxide (iNO)

Electrical Impedance Tomography; Electrical Impedance Tomography and Dual-Energy Computed Tomography

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult intubated and mechanically ventilated patients (≥ 18 years old) admitted to the intensive care unit (ICU)
• ARDS diagnosis with mild to moderate severity by Berlin criteria1 (100 mmHg \< PaO2/FiO2 \<= 300 mmHg)
• Presence of an arterial line for blood gas measurement and blood pressure monitoring and of a central line for hypertonic saline injection

You may not qualify if:

• Suspected pregnancy, pregnancy or less than six weeks postpartum
• Younger than 18 years or older than 80 years
• Baseline methemoglobin ≥ 5%
• Subjects enrolled in another interventional research study
• Presence of pneumothorax
• Usage of any devices with electric current generation, such as a pacemaker or internal cardiac defibrillator
• Preexisting chronic lung disease or pulmonary hypertension
• Past medical history of lung malignancy or pneumonectomy, or lung transplant
• Left ventricle ejection fraction \<20%
• Hemodynamic instability is defined as:
• Persistent systolic blood pressure \<90 mmHg and/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.
• Hypernatremia (serum sodium \> 150 mEq/L)
• Patients cannot be enrolled for DECT if they have:
• History of allergic reaction to intravenous contrast

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (12)

• ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.

  PMID: 22797452 BACKGROUND

• Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, Herridge M, Randolph AG, Calfee CS. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019 Mar 14;5(1):18. doi: 10.1038/s41572-019-0069-0.

  PMID: 30872586 BACKGROUND

• Cressoni M, Caironi P, Polli F, Carlesso E, Chiumello D, Cadringher P, Quintel M, Ranieri VM, Bugedo G, Gattinoni L. Anatomical and functional intrapulmonary shunt in acute respiratory distress syndrome. Crit Care Med. 2008 Mar;36(3):669-75. doi: 10.1097/01.CCM.0000300276.12074.E1.

  PMID: 18091555 BACKGROUND

• Zapol WM, Kobayashi K, Snider MT, Greene R, Laver MB. Vascular obstruction causes pulmonary hypertension in severe acute respiratory failure. Chest. 1977 Feb;71(2 suppl):306-7. doi: 10.1378/chest.71.2_supplement.306. No abstract available.

  PMID: 836381 BACKGROUND

• Greene R, Zapol WM, Snider MT, Reid L, Snow R, O'Connell RS, Novelline RA. Early bedside detection of pulmonary vascular occlusion during acute respiratory failure. Am Rev Respir Dis. 1981 Nov;124(5):593-601. doi: 10.1164/arrd.1981.124.5.593. No abstract available.

  PMID: 7305115 BACKGROUND

• Tomashefski JF Jr, Davies P, Boggis C, Greene R, Zapol WM, Reid LM. The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol. 1983 Jul;112(1):112-26.

  PMID: 6859225 BACKGROUND

• Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med. 1993 Feb 11;328(6):399-405. doi: 10.1056/NEJM199302113280605.

  PMID: 8357359 BACKGROUND

• Johnson TR. Dual-energy CT: general principles. AJR Am J Roentgenol. 2012 Nov;199(5 Suppl):S3-8. doi: 10.2214/AJR.12.9116.

  PMID: 23097165 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

• Safaee Fakhr B, Araujo Morais CC, De Santis Santiago RR, Di Fenza R, Gibson LE, Restrepo PA, Chang MG, Bittner EA, Pinciroli R, Fintelmann FJ, Kacmarek RM, Berra L. Bedside monitoring of lung perfusion by electrical impedance tomography in the time of COVID-19. Br J Anaesth. 2020 Nov;125(5):e434-e436. doi: 10.1016/j.bja.2020.08.001. Epub 2020 Aug 7. No abstract available.

  PMID: 32859359 RESULT

• Morais CCA, Safaee Fakhr B, De Santis Santiago RR, Di Fenza R, Marutani E, Gianni S, Pinciroli R, Kacmarek RM, Berra L. Bedside Electrical Impedance Tomography Unveils Respiratory "Chimera" in COVID-19. Am J Respir Crit Care Med. 2021 Jan 1;203(1):120-121. doi: 10.1164/rccm.202005-1801IM. No abstract available.

  PMID: 33196303 RESULT

• De Santis Santiago R, Teggia Droghi M, Fumagalli J, Marrazzo F, Florio G, Grassi LG, Gomes S, Morais CCA, Ramos OPS, Bottiroli M, Pinciroli R, Imber DA, Bagchi A, Shelton K, Sonny A, Bittner EA, Amato MBP, Kacmarek RM, Berra L; Lung Rescue Team Investigators. High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial. Am J Respir Crit Care Med. 2021 Mar 1;203(5):575-584. doi: 10.1164/rccm.201909-1687OC.

  PMID: 32876469 RESULT

MeSH Terms

Conditions

Respiratory Distress Syndrome; Respiratory Aspiration

Interventions

Fractional Exhaled Nitric Oxide Testing

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Breath Tests; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Maurizio Cereda, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

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: MD, Member of the Faculty of Anaesthesia

Model Details: In a prospective, single-center, physiological, crossover study, the investigators will recruit 70 adults meeting the ARDS criteria based on the Berlin definition who have not previously received inhaled vasodilators.

Study Record Dates

• First Submitted: March 11, 2023
• First Posted: April 6, 2023
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)