NCT04290871

Brief Summary

The investigators will enroll 104 patients with severe COVID-19 infection that mechanical ventilation is needed for respiratory support. Patients will be randomized to receive either inhaled nitric oxide (per protocol) or a placebo. ICU Standards of care will be the institution's own protocols (such as ventilation strategies and use and dose of antivirals and antimicrobials, steroids, inotropic and vasopressor agents).

Trial Health

15
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jan 2023

Shorter than P25 for phase_2

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 27, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 2, 2020

Completed
2.9 years until next milestone

Study Start

First participant enrolled

January 16, 2023

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2023

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2024

Completed
Last Updated

February 8, 2023

Status Verified

February 1, 2023

Enrollment Period

12 months

First QC Date

February 27, 2020

Last Update Submit

February 5, 2023

Conditions

Coronavirus Covid-19 Infection Variant OmicronSARS (Severe Acute Respiratory Syndrome)

Outcome Measures

Primary Outcomes (1)

  • Ventilation free days (VFDs)

    count the days that patients do not need mechanical ventilation

    28 days since beginning of treatment

Secondary Outcomes (8)

  • Survival at 28 days

    28 days

  • Survival at 90 days

    90 days

  • WHO COVID Ordinal Outcomes Scale

    28 days

  • time to improvement of oxygenation

    through oxygenation improvement, an average of 2 days

  • MODS needs life support

    28 days

  • +3 more secondary outcomes

Study Arms (2)

Treatment Group

EXPERIMENTAL

Nitric Oxide gas will be administered in the ventilatory circuit.

Drug: Nitric Oxide Gas

Control Group

SHAM COMPARATOR

The delivery system will be set up anyway without study gas administration

Other: The delivery system will be set up anyway without study gas administration

Interventions

Nitric Oxide GasDRUG

Inspired NO/N2 will be delivered at 80 parts per million (ppm) in the first 48 hours of enrollment (within 48 hours after initiation of mechanical ventilation). Weaning from NO will start after 48-h consecutive NO inhalation. The physicians will follow their own institutional weaning protocols.

Also known as: Nitric Oxide inhalation
Treatment Group
The delivery system will be set up anyway without study gas administrationOTHER

The delivery system will be set up anyway without study gas administration

Control Group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 years
  • Diagnosed Covid-19 infection
  • Severe cases of Covid-19 infection needs mechanical ventilation

You may not qualify if:

  • Physician makes a decision that trial involvement is not in the patient's best interest or any condition that does not allow the protocol to be followed safely
  • Pregnant or positive pregnancy test in a pre-dose examination
  • mechanical ventilation initiated for more than 48 hrs
  • Rescue Use ECMO
  • With severe organ dysfunction or failure (Child Pugh≥12, eGFRC30 ml/min/1.73m2, on RRT or dialysis)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (12)

  • Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.

    PMID: 32031570BACKGROUND

  • Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.

    PMID: 31978945BACKGROUND

  • Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.

    PMID: 32085846BACKGROUND

  • Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24.

    PMID: 32105632BACKGROUND

  • Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, Zhu Y, Hedenstierna G, Wang CG. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin Infect Dis. 2004 Nov 15;39(10):1531-5. doi: 10.1086/425357. Epub 2004 Oct 22.

    PMID: 15546092BACKGROUND

  • Keyaerts E, Vijgen L, Chen L, Maes P, Hedenstierna G, Van Ranst M. Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound. Int J Infect Dis. 2004 Jul;8(4):223-6. doi: 10.1016/j.ijid.2004.04.012.

    PMID: 15234326BACKGROUND

  • Valsecchi C, Winterton D, Safaee Fakhr B, Collier AY, Nozari A, Ortoleva J, Mukerji S, Gibson LE, Carroll RW, Shaefi S, Pinciroli R, La Vita C, Ackman JB, Hohmann E, Arora P, Barth WH Jr, Kaimal A, Ichinose F, Berra L; DELiverly oF iNO (DELFiNO) Network Collaborators. High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia. Obstet Gynecol. 2022 Aug 1;140(2):195-203. doi: 10.1097/AOG.0000000000004847. Epub 2022 Jul 6.

    PMID: 35852269BACKGROUND

  • Fang W, Jiang J, Su L, Shu T, Liu H, Lai S, Ghiladi RA, Wang J. The role of NO in COVID-19 and potential therapeutic strategies. Free Radic Biol Med. 2021 Feb 1;163:153-162. doi: 10.1016/j.freeradbiomed.2020.12.008. Epub 2020 Dec 22.

    PMID: 33347987BACKGROUND

  • Garfield B, McFadyen C, Briar C, Bleakley C, Vlachou A, Baldwin M, Lees N, Price S, Ledot S, McCabe C, Wort SJ, Patel BV, Price LC. Potential for personalised application of inhaled nitric oxide in COVID-19 pneumonia. Br J Anaesth. 2021 Feb;126(2):e72-e75. doi: 10.1016/j.bja.2020.11.006. Epub 2020 Nov 14. No abstract available.

    PMID: 33288208BACKGROUND

  • Montiel V, Lobysheva I, Gerard L, Vermeersch M, Perez-Morga D, Castelein T, Mesland JB, Hantson P, Collienne C, Gruson D, van Dievoet MA, Persu A, Beauloye C, Dechamps M, Belkhir L, Robert A, Derive M, Laterre PF, Danser AHJ, Wittebole X, Balligand JL. Oxidative stress-induced endothelial dysfunction and decreased vascular nitric oxide in COVID-19 patients. EBioMedicine. 2022 Mar;77:103893. doi: 10.1016/j.ebiom.2022.103893. Epub 2022 Feb 23.

    PMID: 35219085BACKGROUND

  • Ghosh A, Joseph B, Anil S. Nitric Oxide in the Management of Respiratory Consequences in COVID-19: A Scoping Review of a Different Treatment Approach. Cureus. 2022 Apr 5;14(4):e23852. doi: 10.7759/cureus.23852. eCollection 2022 Apr.

    PMID: 35530860BACKGROUND

  • Al Sulaiman K, Korayem GB, Altebainawi AF, Al Harbi S, Alissa A, Alharthi A, Kensara R, Alfahed A, Vishwakarma R, Al Haji H, Almohaimid N, Al Zumai O, Alrubayan F, Asiri A, Alkahtani N, Alolayan A, Alsohimi S, Melibari N, Almagthali A, Aljahdali S, Alenazi AA, Alsaeedi AS, Al Ghamdi G, Al Faris O, Alqahtani J, Al Qahtani J, Alshammari KA, Alshammari KI, Aljuhani O. Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: a multicenter cohort study. Crit Care. 2022 Oct 3;26(1):304. doi: 10.1186/s13054-022-04158-y.

    PMID: 36192801RESULT

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome

Interventions

Endothelium-Dependent Relaxing Factors

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsVirus DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vasodilator AgentsCardiovascular AgentsTherapeutic UsesPharmacologic ActionsChemical Actions and Uses

Study Officials

  • Chong Lei, MD, PhD

    Air Force Military Medical University, China

    PRINCIPAL INVESTIGATOR

  • Lorenzo Berra, MD

    Massachusetts General Hospital

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

February 27, 2020

First Posted

March 2, 2020

Study Start

January 16, 2023

Primary Completion

December 31, 2023

Study Completion

April 1, 2024

Last Updated

February 8, 2023

Record last verified: 2023-02