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Acute Respiratory Distress SyndromeNCT05801224

Vascular ARDS Recruitment After Inhaled Nitric Oxide

A study testing Nitric Oxide in people with Acute Respiratory Distress Syndrome and Ventilation Perfusion Mismatch, run by Massachusetts General Hospital at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Nitric Oxide
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteUnited States
Study dates
10 Jul 2026to 31 Dec 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • Suspected pregnancy, pregnancy or less than six weeks postpartum
  • Younger than 18 years or older than 80 years
  • Patients with thorax perimeter not within the range of 37.5 - 134cm
  • Baseline methemoglobin ≥ 5%
  • Hemoglobin level less than 7 g/dl
  • Subjects enrolled in another interventional research study
Show all 22Show fewer
  • Presence of pneumothorax
  • Usage of any devices with the electric current generation, such as a pacemaker or internal cardiac defibrillator
  • Past medical history of severe lung disease
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Cytochrome b5 reductase deficiency
  • Sickle cell disease
  • Patients that are receiving inhaled pulmonary vasodilators at the time of the enrollment
  • 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.
  • Increase in FiO2 > 20%, increase in PEEP > 5cmH2O over the past two hours just before enrollment
  • Hypernatremia (serum sodium > 150 mEq/L)
  • Patients cannot be enrolled for DECT if they have:
  • History of allergic reaction to intravenous contrast
  • Renal dysfunction on the day of the study (serum creatinine > 1.5 mg/dL)
  • Limited to sub-cohort 2: contraindications to prone positioning.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Maurizio F Cereda, MD contact

6177263030

mcereda@mgh.harvard.edu

Roberta Ribeiro De Santis Santiago, MD, PhD contact

6176437733

rrsantiago@mgh.harvard.edu

United States1 site, 1 recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Maurizio Cereda, 6177263030, MCEREDA@mgh.harvard.edu

    Roberta Ribeiro De Santis Santiago, 6176437733, rrsantiago@mgh.harvard.edu

    Recruiting

Other trials in United States

About this study

Official title: Regional Vascular Recruitment With Inhaled Nitric Oxide in Patients With ARDS

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.

Prone position has been used for several years in the care of ARDS patients and has been demonstrated to improve survival in more severe patients. It is not known how iNO and prone positioning interact in determining the distribution of pulmonary perfusion and whether their combine use can benefit ARDS patients.

Read more

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 and to prone positioning utilizing EIT. The main questions it aims to answer are:

  1. If EIT can measure lung regional perfusion response to an iNO challenge of 20ppm for 15 minutes.
  2. If EIT can measure the lung regional perfusion responses to prone position, applied alone and in combination with iNO.
  3. If EIT is comparable to dual-energy computed tomography (DECT), the gold-standard method, in the detection of changes in regional lung perfusion due to iNO.
  4. If EIT can be an imaging marker to identify ARDS severity

Participants will be divided into three cohorts:

  1. Sub-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) in the supine position
  2. Sub-Cohort 2 (N=10): Participants will be asked to be monitored by EIT before and during the administration of iNO (20 ppm) for 15 minutes (OFF-ON) in both the supine and in the prone position. The same subjects will be monitored also with DECT in the supine position and then after 30 minutes in the prone position (without NO administration).
  3. Sub-Cohort 3 (N=10): In this subset of Sub-Cohort 1, subjects will be asked to be monitored also with DECT (in addition to EIT) in the supine body position before iNO and after 15 minutes while receiving iNO.
Read the detailed description

The investigators will screen patients with ARDS diagnosis daily at MGH intensive care units and work in the consenting process with the ICU team and surrogates. The enrollment period will be limited to the time subjects will undergo the study procedures. Subjects will exit the study as soon as the study procedures are completed. No further procedures are planned; therefore, subjects will not be asked to return to the hospital exclusively for research-related purposes.

The enrolled subjects (n=70) will be divided into three sub-cohorts. Sub-Cohort 1 (n=60) will be monitored with EIT before, during, and after the administration of iNO (OFF-ON-OFF). Sub-Cohort 2 (n=10) will be monitored with EIT before and during the administration of iNO (OFF-ON) in the supine and in the prone position, and with DECT in the supine and in the prone position (without iNO). Sub-Cohort 3 (n=10) will be a subset of Cohort 1 and will be monitored with DECT before and during the administration of iNO, in addition to EIT monitoring before, during and after iNO administration (OFF-ON-OFF).

Methods to answer question 1 (To measure the topographic perfusion response to an iNO challenge with EIT):

  • The EIT monitoring will be composed of ventilation and perfusion distributions. First, the ventilation is recorded; at this point, no additional maneuver is needed; the subjects need to wear the electrode belt connected to the device, and their ventilation will be recorded. Secondly, for the perfusion distribution, after a pause in the ventilation, EIT measures the distribution of blood perfusion in the lungs during the injection of a 10 mL bolus of 11.7% hypertonic saline solution through a central venous catheter. Cohort 1 (n=60) will receive 20ppm of iNO for 15 minutes. Cohort 1 will be monitored with EIT before, during, and after the iNO delivery in an OFF-ON-OFF fashion.

Methods to answer question 2 (To measure the topographic perfusion response to prone position, applied alone and in combination with iNO):

  • Sub-Cohort 2 (n=10) will be monitored with EIT before and after 15 minutes receiving 20ppm iNO in an OFF-ON fashion, both in the supine and in the prone position. A second EIT measurement off iNO will not be obtained to minimize the total dose of hypertonic saline solution. The subjects will be transported to the computed tomography (CT) room, and DECT will be performed first in the supine position. A second DECT will be obtained after 30 minutes in the prone position. No iNO will be given during DECT.

Methods to answer question 3 (To compare changes of regional lung perfusion due to iNO detected by EIT against the changes detected by gold standard DECT):

  • 10 subjects in Sub-Cohort 1 will receive DECT in addition to EIT monitoring in the supine position. DECT will be obtained before the iNO delivery. Then, the iNO delivery will start, and after 15 minutes, DECT will be repeated.

Methods to answer question 4 (to define correlations between EIT-derived perfusion changes during an iNO challenge and clinical characteristics and outcomes. ):

  • The investigators will explore the vascular response measured by EIT from all 70 subjects and categorize subjects accordingly. The investigators plan to apply EIT patterns as an image marker and use them in conjunction with other markers (demographical, radiological, clinical, biochemical, and inflammatory) to identify ARDS severity.

Finally,

  • Blood MetHb levels will be continuously monitored before, during, and after each iNO administration of the day. At the end of each iNO administration, MetHb will continue to be monitored until values return to the level recorded before the current treatment and
  • The NO, nitrogen dioxide (NO2) will be continuously monitored by INOmax DSIR (Mallinckrodt) deliver system.
Being tested
Nitric Oxide
Keywords
Acute respiratory distress syndrome, Ventilation/perfusion mismatch, Electrical impedance tomography, Inhaled nitric oxide, Dual-energy computed tomography
Medical subject headings
Respiratory Distress Syndrome, Respiratory Aspiration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nitric OxideDevice

    Also called inhaled nitric oxide (iNO)

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

Study groups in NCT05801224
Study groupRoleWhat they receive
Electrical Impedance TomographyExperimentalA total of 60 subjects (Sub-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.
Receives: Device: Nitric Oxide
Electrical Impedance Tomography and Dual-Energy Computed Tomography in the Supine and Prone positionExperimentalIn a subset of 10 subjects (Sub-Cohort 2), EIT will be performed without and with iNO (OFF-ON) both in the supine and in the prone position. The OFF-ON fashion for EIT imaging is to minimize the subject's exposure to hypertonic saline solution. Sub-cohort 2 patient will be imaged also with DECT in the supine and after 30 minutes in the prone position. iNO will not be administered during DECT.
Receives: Device: Nitric Oxide
Electrical Impedance Tomography with and without Inhaled Nitric Oxide in the Supine PositionExperimental10 subjects (Sub-Cohort 3) from Sub-Cohort 1 will be monitored without iNO, with iNO, and without iNO (OFF-ON-OFF) in the supine position. Sub-Cohort 3 subjects will be imaged also with DECT. Imaging will be performed in the supine position without iNO and following iNO administration for 15 minutes (OFF-ON) .
Receives: Device: Nitric Oxide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Day 1

Secondary outcomes (1)

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

    The secondary outcome is to To compare electrical impedance tomography measurements against the gold standard dual-energy computed tomography (DECT)

    Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Apr 2023
  2. Study start10 Jul 2026
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05801224
Sponsor's protocol ID
2023p000138
Status last verified
Sep 2026
First submitted
11 Mar 2023
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 22797452

  • 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.

    PubMed 30872586

  • 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.

    PubMed 18091555

  • 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.

    PubMed 836381

  • 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.

    PubMed 7305115

  • 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.

    PubMed 6859225

  • 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.

    PubMed 8357359

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

    PubMed 23097165

  • 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.

    PubMed 21960654

  • 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.

    PubMed 32859359

  • 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.

    PubMed 33196303

  • 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.

    PubMed 32876469

Questions about this trial

What is this clinical trial studying?

A study testing Nitric Oxide in people with Acute Respiratory Distress Syndrome and Ventilation Perfusion Mismatch, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Maurizio F Cereda, MD (6177263030, mcereda@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in regional lung perfusion after the delivery of inhaled nitric oxide (time frame: Day 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05801224, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.

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