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Bronchiolitis AcutePhase 2NCT04060979

Evaluation of Two Doses of Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis

A Phase 2 study testing Nitric Oxide and Standard Supportive treatment in people with Bronchiolitis Acute, run by Beyond Air Inc. at 7 sites in Israel.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Prospective, Double-Blinded, Randomized, Multi-Center Study for Evaluation of Two Doses of Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis The proposed study judiciously expands these observations for use of NO treatment in pediatric patients with bronchiolitis aged less than 12… Read more about this study

Who is it for?
Ages 1 day to 12 months
Conditions the study is for
Bronchiolitis Acute
What is being tested?
Nitric Oxide and Standard Supportive treatment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
7 sitesIsrael
Study dates
6 Nov 2019to 2 Apr 2020
Phase
Phase 2
Are there results?
None posted in the registry

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 1 day to 12 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Pediatric subjects up to 12-months of age, including subjects born ≥ 28 weeks of gestation.
  • Subjects with acute bronchiolitis requiring in-patient hospitalization expected to last 24 hours or more.
  • Modified Tal Score (mTal) between 7 to 10 at screening. Note that the oxygen requirement section of the clinical score reflects patient's oxygen saturation without oxygen supplementation.
  • Screening SpO2 of 92% or less in room-air
  • A parent/guardian who is willing to comply with the study procedures and signs an informed consent on behalf of the subject.

Who cannot join

  • Subjects diagnosed with alveolar pneumonia by chest X-ray and white blood cell (WBC)≥ 15,000/ul and Temp >39°C
  • Previous diagnosis of asthma or cough lasting more than 4 weeks or chronic requirement for asthma medications.
  • Subjects with 2 or more previous physician diagnosed wheezing episodes.
  • Any previous intensive care unit admission for respiratory distress or respiratory-related illness
  • Diagnosis of Bronchopulmonary Dysplasia (BPD) based on medical history and home oxygen use.
  • Subjects on home oxygen use for any reason
Show all 37Show fewer
  • Presence or use of a nasogastric or orogastric feeding tube
  • Subjects with history of methemoglobinemia, known hereditary methemoglobinemia, and/or methemoglobin >2% for any cause.
  • Use of an investigational drug or device within 30 days before enrollment and/or expected to participate in a new study within 90 days of enrollment.
  • History of frequent epistaxis (>1 episode/month) or significant hemoptysis within 30 days prior to enrollment (≥5 mL of blood in one coughing episode)
  • Taken medications such as chronic systemic corticosteroids, central nervous system (CNS) stimulants, theophylline or aminophylline, anti-arrhythmic within 30 days of screening.
  • Diagnosed with an underlying condition, which significantly affects respiratory system:
  • Cystic fibrosis (CF), primary ciliary dyskinesia, non-CF bronchiectasis
  • Immune deficiency
  • Genetic or neurological disorder capable of causing:
  • Impaired respiratory secretions clearance including insufficient cough
  • chronic respiratory failure and insufficiency
  • restrictive lung disease
  • Conditions that decrease the muscle strength
  • Glucose 6-phosphate dehydrogenase deficiency
  • 6-Phosphogluconate dehydrogenase deficiency
  • Trisomy 21 (Down Syndrome)
  • Presence of upper airway anomalies that may interfere with breathing, including:
  • Choanal atresia or stenosis
  • Cleft lip and palate
  • Tracheo-esophageal fistula
  • Tracheal stenosis
  • Tracheomalacia and/or bronchomalacia
  • History of severe aspiration pneumonia
  • Having the following signs or symptoms:
  • clinically significant pulmonary (lung) and/or cardiac (heart) congenital malformations
  • an underlying renal, or liver insufficiency, immunodeficiency, encephalopathy;
  • known or suspected foreign body aspiration during enrollment.
  • If the first treatment cannot start within 6 hours after signing of the informed consent form (ICF), the subject is not eligible for enrollment.
  • Symptoms (i.e., cough and wheezing) started longer than 72 h before admission to the hospital
  • Per Investigator's discretion, the subject parents/legal guardian(s) are unable to comply with the study procedures.
  • Any reason that, in the opinion of the investigator, may make the subject unfit for this clinical trial.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Israel7 sites
  • Haemek Medical Center

    Afula

  • Assuta Ashdod

    Ashdod

  • Soroka Medical Center

    Beersheba

  • Carmel MEdical Center

    Haifa

  • Shaarei Zedek Medical Center

    Jerusalem

  • Schneider Children's hospital

    Petah Tikva

  • Sheba Medical Center

    Tel HaShomer

Other trials in Israel

About this study

Official title: Prospective, Double-Blinded, Randomized, Multi-Center Study for Evaluation of Two Doses of Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis

Prospective, Double-Blinded, Randomized, Multi-Center Study for Evaluation of Two Doses of Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis

The proposed study judiciously expands these observations for use of NO treatment in pediatric patients with bronchiolitis aged less than 12 months. The intermittent dosing strategy used in this study has been selected to minimize the potential for adverse effects. The inclusion of two doses in the proposed pilot study is intended to determine a dose response effect and select a dose that is optimally safe and effective. The primary endpoint evaluation of time to fit for discharge will provide an effective objective measurement for the treatment effectiveness compared to standard supportive treatment of bronchiolitis.

Read more

Primary objective:

  • Assess whether Nitric Oxide (NO) administered intermittently in 2 concentrations (via inhalation for 40 minutes 4 times per day for up to 5 consecutive days) in addition to Standard Supportive Treatment (SST) shortens the recovery time of infants with bronchiolitis, compared to SST alone.

Secondary objectives:

  • Time to achieve O2 saturation of ≥ 92 % sustained for at least 2 hours
  • Reduction in hospital Length of Stay (LOS)
  • Time to achieve mTal score of ≤ 5

Safety objectives: Characterize the safety of 2 doses of NO intermittent inhalation treatment therapy as measured by Adverse Events (AE) - number and percentage of subjects that experience AEs - and Serious Adverse Events (SAEs).

A total of 90 subjects will be enrolled into the study and randomized in a 1:1:1 ratio to receive the study treatments.

Treatment administration: Treatment blindness will be kept by designation of blinded and un-blinded team members.The blinded staff will be performing the study assessment procedures and the un-blinded team will be administering the actual treatment.

Subjects' parents/legal guardian will be contacted for a follow up phone call at days 14+5 and 30+5 from the date of enrollment of the subject into the study.

Read the detailed description

Prospective, Double-Blinded, Randomized, Multi-Center Study for Evaluation of Two Doses of Nitric Oxide (NO) Given Intermittently Via Inhalation to Subjects With Bronchiolitis

Bronchiolitis is a viral disease, widely spread amongst young children with significant mortality in some cases and no specific treatment available, besides supportive treatment of O2 and hydration; therefore, there is an identified unmet medical need to develop a treatment strategy for children with bronchiolitis.

When the immune system's NO generating ability is overwhelmed or compromised, infection and disease occur. Increasing the body's ability to produce more NO through gene therapy or synthetic NO donor drugs is of interest in medicine.

NO, by itself, is an essential part of the innate defense mechanism of the human immune system which becomes up-regulated by the inducible NO synthase (iNOS) during various inflammatory conditions and during microbial and viral infections. This suggests that NO treatment in appropriate concentrations is highly relevant for children with bronchiolitis.

The two previous pilot studies conducted by Beyond Air (formerly known as AIT) found that intermittent exposure to was safe and well tolerated in pediatric subjects with acute bronchiolitis age 0-12 months and showed a trend in reduction in the length of hospitalization. The overall frequency of adverse events was found to be similar between the control and NO treated groups and intermittent exposure at 160 ppm did not result in exposure to unsafe Nitric Dioxide (NO2) levels or had a cumulative effect on MetHb levels.

The proposed study judiciously expands these observations for use of NO treatment in pediatric patients with bronchiolitis aged less than 12 months. The intermittent dosing strategy used in this study has been selected to minimize the potential for adverse effects. The inclusion of two doses in the proposed pilot study is intended to determine a dose response effect and select a dose that is optimally safe and effective. The primary endpoint evaluation of time to fit for discharge will provide an effective objective measurement for the treatment effectiveness compared to standard supportive treatment of bronchiolitis.

NO therapy can be cost effective, technologically simple and easily adaptive for use in inhaled pulmonary infections. Ultimately, therapeutic use of NO could be the initial treatment by mimicking the body's natural first line method to fight infections. Together, these results and rationale warrant the need to accelerate research of NO as a potential solution for front line treatment for bronchiolitis.

Primary objective:

  • Assess whether Nitric Oxide (NO) administered intermittently in 2 concentrations (via inhalation for 40 minutes 4 times per day for up to 5 consecutive days) in addition to Standard Supportive Treatment (SST) shortens the recovery time of infants with bronchiolitis, compared to SST alone.

Secondary objectives:

  • Time to achieve O2 saturation of ≥ 92 % sustained for at least 2 hours
  • Reduction in hospital Length of Stay (LOS)
  • Time to achieve mTal score of ≤ 5

Safety objectives: Characterize the safety of 2 doses of NO intermittent inhalation treatment therapy as measured by Adverse Events (AE) - number and percentage of subjects that experience AEs - and Serious Adverse Events (SAEs).

A total of 90 subjects will be enrolled into the study and randomized in a 1:1:1 ratio to receive the study treatments.

Treatment administration: Treatment blindness will be kept by designation of blinded and un-blinded team members.The blinded staff will be performing the study assessment procedures and the un-blinded team will be administering the actual treatment.

Subjects' parents/legal guardian will be contacted for a follow up phone call at days 14+5 and 30+5 from the date of enrollment of the subject into the study.

Being tested
Nitric Oxide, Standard Supportive treatment

What participants receive

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

  • Nitric OxideDrug

    Nitric Oxide given intermittently via inhalation

  • Standard Supportive treatmentOther

    Standard Supportive treatment (including oxygen)

Study groups in NCT04060979
Study groupRoleWhat they receive
Group 1- NO treatment- dose 1ExperimentalWill comprise of approximately 30 patients and will receive inhalations of dose 1 of NO combined with O2/air for 40 minutes, every 4.5 hours during the day four times a day for up to 5 days in addition to standard supportive treatment.
Receives: Drug: Nitric Oxide; Other: Standard Supportive treatment
Group 2- NO treatment- dose 2ExperimentalWill comprise of approximately 30 patients and will receive inhalations of dose 2 of NO combined with O2/air for 40 minutes, every 4.5 hours during the day four times a day for up to 5 days in addition to standard supportive treatment.
Receives: Drug: Nitric Oxide; Other: Standard Supportive treatment
Group 3- Control treatmentOtherWill comprise of approximately 30 patients and will receive O2/air using the same treatment schedule and equipment as groups 1 and 2, in addition to standard supportive treatment.
Receives: Other: Standard Supportive treatment

What is being measured

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

  1. Time to "fit for discharge"

    Time to "fit for discharge". "Fit for discharge" is a composite endpoint measured by the following:

    • Achieving Modified Tal score [mTal] ≤ 5 And
    • Oxygen saturation (SpO2) ≥92% at room air (without oxygen supplementation) sustained for at least 2 hours Both of these will be determined from the time of enrollment (when the ICF is signed).

    Measured: up to 14 days

Secondary outcomes (4)
  1. Time to achieve O2 saturation of ≥ 92 %. sustained for at least 2 hours

    The time in hours calculated from the time of patient's enrollment until the time required to achieve the endpoint.

    Measured: up to 14 days

  2. Hospital Length of Stay (LOS)

    LOS is measured in hours from the time of patient's enrollment in the study until the physician's order to discharge from the hospital. A patient will be evaluated for discharge from the hospital only after meeting the primary efficacy endpoint.

    Measured: up to 14 days

  3. Modified Tal score [mTal] ≤5

    The time in hours calculated from the time of patient's enrollment until the time required to achieve a clinical score of less than or equal to 5.

    Measured: up to 14 days

  4. Incidence of Treatment-Emergent Adverse Events

    Number of treatment-emergent adverse events (AEs) and Serious AEs

    Measured: Baseline to 30 days post dose

Timeline

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

  1. First posted19 Aug 2019
  2. Study start6 Nov 2019
  3. Primary completion2 Mar 2020
  4. Study completion2 Apr 2020

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04060979
Sponsor's protocol ID
AIT_CP_BRONC_03.01
Status last verified
Jan 2020
First submitted
11 Aug 2019
Last updated
12 May 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Goldbart A, Lavie M, Lubetzky R, Pillar G, Landau D, Schlesinger Y, Spiegel R, Golan-Tripto I, Nahum A, Greenberg D, Tal A. Inhaled Nitric Oxide for the Treatment of Acute Bronchiolitis: A Multicenter Randomized Controlled Clinical Trial to Evaluate Dose Response. Ann Am Thorac Soc. 2023 Feb;20(2):236-244. doi: 10.1513/AnnalsATS.202103-348OC.

    PubMed 36169967

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nitric Oxide and Standard Supportive treatment in people with Bronchiolitis Acute, run by Beyond Air Inc. at 7 sites in Israel.

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 5 inclusion and 37 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: finished, as of the sponsor's last update on 12 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Israel. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to "fit for discharge" (time frame: up to 14 days). 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 NCT04060979, which also lists 1 linked publication.

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 12 May 2020.

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