BronchiolitisPhase 3NCT03053388
Evaluation of the Efficacy Safety and Tolerability of Nitric Oxide Given Intermittently Via Inhalation to Subjects With Bronchiolitis
A Phase 3 study testing Nitric Oxide and Supportive treatment in people with Bronchiolitis, run by Beyond Air Inc. at 10 sites in Israel.
Trial summary
Double blind, randomized multi-center, evaluation of the efficacy, safety and tolerability of Nitric Oxide (NO) given intermittently via inhalation to subjects with acute bronchiolitis. Bronchiolitis is defined as an infection of the small airways. Read more about this study
- Who is it for?
- Ages Up to 12 months
- Conditions the study is for
- Bronchiolitis
- What is being tested?
- Nitric Oxide and Supportive treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 10 sitesIsrael
- Study dates
- 5 Mar 2017to 28 Apr 2018
- Phase
- Phase 3
- 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 Up to 12 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 1. Pediatric subjects 0-12-months old.
- Including subjects born at ≥28 weeks of gestation.
- Subjects with acute bronchiolitis requiring in-patient hospitalization expected for 24 hours and more.
- Clinical score of between 7 to 10 at Screening (without oxygen supplementation).
- Parent/guardian who is willing and able to sign, an informed consent on behalf of the subject.
Who cannot join
- 1. Subjects diagnosed with alveolar pneumonia on Chest X-ray (including WBC≥ 15,000/ul, and Temp >39°C).
- Previous diagnosis of asthma or requirement for asthma medications.
- Subjects with >2 previous wheezing episodes.
- History of life-threatening respiratory distress that requires admission to an intensive care unit for treatment.
- Subjects with history of methemoglobinemia and/or methemoglobin >5% for any cause.
- Use of an investigational drug within 30 days before enrolment and/or expected to participate in a new study within 90 days.
Show all 12Show fewer
- History of frequent epistaxis (>1 episode/month) or significant hemoptysis within 30 days prior to enrolment (≥5 mL of blood in one coughing episode or >30 mL of blood in a 24-hour period.
- Taken medications such as chronic systemic corticosteroids, CNS stimulants, theophylline or aminophylline, anti-arrhythmic within a certain time period prior to the study.
- Unable to comply with the study procedures.
- Underlying genetic disorders (including Cystic fibrosis) or hypotonia.
- Having the following signs or symptoms: 1) known pulmonary (lung) and/or cardiac (heart) congenital malformations 2) an underlying renal, or liver insufficiency, immunodeficiency, encephalopathy; 3) known or suspected foreign body aspiration.
- Any reason that, in the opinion of the investigator, may make the subject unfit for this clinical trial.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Israel10 sites
Haemek Medical Center
Afula
Barzili Medical Center
Ashkelon
Soroka Medical Center
Beersheba
Carmel Medical Center
Haifa
Rambam Medical Center
Haifa
Hadassah Medical Center
Jerusalem
Schneider Children's Hospital
Petah Tikva
Sheba Medical Center
Ramat Gan
Kaplan Medical Center
Rehovot
Tel-Aviv Sourasky Medical Center
Tel Aviv
About this study
Double blind, randomized multi-center, evaluation of the efficacy, safety and tolerability of Nitric Oxide (NO) given intermittently via inhalation to subjects with acute bronchiolitis.
Bronchiolitis is defined as an infection of the small airways. It is also the most common manifestation of acute lower respiratory infection (ALRI) in early infancy, and is the leading cause of global child mortality.
Read more
Nitric Oxide (NO) has been shown to play a critical role in various biological functions, including in the vasodilatation of smooth muscle, neurotransmission, regulation of wound healing and during immune responses to infection with a microbicidal action directed toward various organisms. In the airways, NO is considered to play a key role in the innate immune system in which the first-line of host defense against microbes is built.
The beneficial effect of NO has been shown in different diseases with several options of doses and regimens; newborn with primary pulmonary hypertension showed improvement in oxygenation after 30 minutes of NO treatment at 10-20 ppm, while subjects with adult respiratory distress syndrome demonstrated clinical improvement during NO treatment at 18 and 36 ppm.
In vitro studies suggested that NO, in part per million (ppm) concentrations, possesses antimicrobial and anti-viral activity against a wide variety of phyla including bacteria, viruses, helminthes and parasites.
Safety and tolerability of 160 ppm NO given intermittently via inhalation were shown in a phase II study performed on 2-12 month infants hospitalized with bronchiolitis. According to data no difference in the proportion of adverse events and serious adverse events were detected between subjects treated with NO and subjects treated with standard supportive treatment.
In this study the investigators wish to assess the efficacy of 160 ppm NO given intermittently via inhalation to 0-12 months-old infants hospitalized due to acute bronchiolitis.
Primary objective: Asses the difference in hospital Length of Stay (LOS) between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment.
Secondary objectives: Asses the difference in the time required to achieve clinical improvement, a clinical score ≤5 (Modified Tal score) between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment. Assess the difference in the time required to achieve sustained 92% oxygen saturation in room air between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment. Characterize the safety and tolerability of 160 ppm NO intermittent inhalation treatment as measure by the rate of adverse events.
In this prospective double-blind, randomized multi-Center study the investigators will enroll up to 120 (no less than 80) subjects aged 0-12 months-old, diagnosed with acute bronchiolitis and requiring in-patient hospitalization.
Enrolled subjects will be randomized into 2 groups. Group 1 -Treatment group - Will receive 160 ppm NO given intermittent via inhalation in addition to standard treatment for up to 5 days. Group 2 - will receive ongoing inhalation of the standard treatment for up to 5 days. Between study and after completing all study inhalations the subject will continue to receive the standard treatment. Oxygen (O2), NO, nitrogen dioxide (NO2) and fraction of inspired oxygen (FiO2) delivered to the patient will be continuously monitored.
Treatment administration: Treatment blindness will be kept by separating between un-blinded team members (giving the actual treatment) and blinded team members, and by hiding the NO container and all study related equipment behind a curtain.
All subjects will return for follow-up visits on day 14(+5), 21(+5) days and will be contacted on day 30 (+5) from day of admission to the department.
- Conditions
- Bronchiolitis
- Being tested
- Nitric Oxide, Supportive treatment
- Medical subject headings
- Bronchiolitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
Nitric Oxide given via inhalation in cycles
Supportive treatmentOther
Supportive treatment (including oxygen)
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - Nitric Oxide treatment | Experimental | • Group 1 (NO treatment) - will receive inhalations of 160 ppm NO combined with O2/air for 30 minutes, every 3-4.5 hours, five times a day (24 hours), for up to 5 days (maximum 25 inhalations), in addition to standard supportive treatment. Receives: Drug: Nitric Oxide; Other: Supportive treatment |
| Group 2 - Control treatment | Active comparator | • Group 2 (Control) - will receive inhalations O2/air using the same treatment schedule and equipment as group 1, in addition to standard supportive treatment. Receives: Other: Supportive treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hospital Length of Stay (LOS)
LOS is measured in hours from the time of first treatment dose to the time of physician decision to discharge.
Measured: 12 days
Secondary outcomes (3)
Clinical score of ≤5 (Modified Tal score).
The time in hours from first treatment dose, required to achieve a clinical score of ≤5.
Measured: 12 days
Oxygen saturation (SaO2) ≥92% in room air (without oxygen supplementation) sustained for at least 2 hours
The time in hours from first treatment dose, required to achieve SaO2 ≥92% in room air sustained for at least 2 hours.
Measured: 12 days
Adverse events and NO-related adverse events including methemoglobinemia and nitrogen dioxide levels.
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2017
- Study start5 Mar 2017
- Primary completion28 Apr 2018
- Study completion28 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BronchiolitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beyond Air Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03053388
- Sponsor's protocol ID
- AIT_CP_BRONC02.01
- Status last verified
- Feb 2017
- First submitted
- 12 Feb 2017
- Last updated
- 9 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Goldbart A, Golan-Tripto I, Pillar G, Livnat-Levanon G, Efrati O, Spiegel R, Lubetzky R, Lavie M, Carmon L, Ghaffari A, Nahum A. Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial. Sci Rep. 2020 Jun 15;10(1):9605. doi: 10.1038/s41598-020-66433-8.
PubMed 32541773
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy Safety and Tolerability of Nitric Oxide Given Intermittently Via Inhalation to Subjects With Bronchiolitis
- ClinicalTrials.gov ID
- NCT03053388
- Acronym / sponsor ID
- AIT_CP_BRONC02.01
- Conditions
- Bronchiolitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Beyond Air Inc.Industry (pharma, biotech, devices)
- Study start
- 5 Mar 2017 (actual)
- Primary completion
- 28 Apr 2018 (actual)
- Study completion
- 28 Apr 2018 (actual)
- First posted
- 15 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Double blind, randomized multi-center, evaluation of the efficacy, safety and tolerability of Nitric Oxide (NO) given intermittently via inhalation to subjects with acute bronchiolitis.
Bronchiolitis is defined as an infection of the small airways. It is also the most common manifestation of acute lower respiratory infection (ALRI) in early infancy, and is the leading cause of global child mortality.
Nitric Oxide (NO) has been shown to play a critical role in various biological functions, including in the vasodilatation of smooth muscle, neurotransmission, regulation of wound healing and during immune responses to infection with a microbicidal action directed toward various organisms. In the airways, NO is considered to play a key role in the innate immune system in which the first-line of host defense against microbes is built.
The beneficial effect of NO has been shown in different diseases with several options of doses and regimens; newborn with primary pulmonary hypertension showed improvement in oxygenation after 30 minutes of NO treatment at 10-20 ppm, while subjects with adult respiratory distress syndrome demonstrated clinical improvement during NO treatment at 18 and 36 ppm.
In vitro studies suggested that NO, in part per million (ppm) concentrations, possesses antimicrobial and anti-viral activity against a wide variety of phyla including bacteria, viruses, helminthes and parasites.
Safety and tolerability of 160 ppm NO given intermittently via inhalation were shown in a phase II study performed on 2-12 month infants hospitalized with bronchiolitis. According to data no difference in the proportion of adverse events and serious adverse events were detected between subjects treated with NO and subjects treated with standard supportive treatment.
In this study the investigators wish to assess the efficacy of 160 ppm NO given intermittently via inhalation to 0-12 months-old infants hospitalized due to acute bronchiolitis.
Primary objective: Asses the difference in hospital Length of Stay (LOS) between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment.
Secondary objectives: Asses the difference in the time required to achieve clinical improvement, a clinical score ≤5 (Modified Tal score) between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment. Assess the difference in the time required to achieve sustained 92% oxygen saturation in room air between subjects treated with 160 ppm NO combined with standard supportive treatment and subjects treated with standard supportive treatment. Characterize the safety and tolerability of 160 ppm NO intermittent inhalation treatment as measure by the rate of adverse events.
In this prospective double-blind, randomized multi-Center study the investigators will enroll up to 120 (no less than 80) subjects aged 0-12 months-old, diagnosed with acute bronchiolitis and requiring in-patient hospitalization.
Enrolled subjects will be randomized into 2 groups. Group 1 -Treatment group - Will receive 160 ppm NO given intermittent via inhalation in addition to standard treatment for up to 5 days. Group 2 - will receive ongoing inhalation of the standard treatment for up to 5 days. Between study and after completing all study inhalations the subject will continue to receive the standard treatment. Oxygen (O2), NO, nitrogen dioxide (NO2) and fraction of inspired oxygen (FiO2) delivered to the patient will be continuously monitored.
Treatment administration: Treatment blindness will be kept by separating between un-blinded team members (giving the actual treatment) and blinded team members, and by hiding the NO container and all study related equipment behind a curtain.
All subjects will return for follow-up visits on day 14(+5), 21(+5) days and will be contacted on day 30 (+5) from day of admission to the department.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 - Nitric Oxide treatment | Experimental | Drug: Nitric Oxide, Other: Supportive treatment• Group 1 (NO treatment) - will receive inhalations of 160 ppm NO combined with O2/air for 30 minutes, every 3-4.5 hours, five times a day (24 hours), for up to 5 days (maximum 25 inhalations), in addition to standard supportive treatment. |
| Group 2 - Control treatment | Active comparator | Other: Supportive treatment• Group 2 (Control) - will receive inhalations O2/air using the same treatment schedule and equipment as group 1, in addition to standard supportive treatment. |
Who may qualify
- Ages
- Up to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 1. Pediatric subjects 0-12-months old.
- Subjects with acute bronchiolitis requiring in-patient hospitalization expected for 24 hours and more.
- Clinical score of between 7 to 10 at Screening (without oxygen supplementation).
- Parent/guardian who is willing and able to sign, an informed consent on behalf of the subject.
Key exclusion criteria (12 listed)
- 1. Subjects diagnosed with alveolar pneumonia on Chest X-ray (including WBC≥ 15,000/ul, and Temp >39°C).
- Previous diagnosis of asthma or requirement for asthma medications.
- Subjects with >2 previous wheezing episodes.
- History of life-threatening respiratory distress that requires admission to an intensive care unit for treatment.
- Subjects with history of methemoglobinemia and/or methemoglobin >5% for any cause.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitric OxideNitric Oxide given via inhalation in cycles | Drug | Group 1 - Nitric Oxide treatment |
| Supportive treatmentSupportive treatment (including oxygen) | Other | Group 1 - Nitric Oxide treatment, Group 2 - Control treatment |
Primary outcome
Hospital Length of Stay (LOS)
Time frame: 12 days
LOS is measured in hours from the time of first treatment dose to the time of physician decision to discharge.
3 secondary outcomes
Clinical score of ≤5 (Modified Tal score).
Time frame: 12 days
Oxygen saturation (SaO2) ≥92% in room air (without oxygen supplementation) sustained for at least 2 hours
Time frame: 12 days
Adverse events and NO-related adverse events including methemoglobinemia and nitrogen dioxide levels.
Time frame: 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2019.
- Derived from this study: PubMed 32541773Goldbart A, Golan-Tripto I, Pillar G, Livnat-Levanon G, Efrati O, Spiegel R, Lubetzky R, Lavie M, Carmon L, Ghaffari A, Nahum A. Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial. Sci Rep. 2020 Jun 15;10(1):9605. doi: 10.1038/s41598-020-66433-8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nitric Oxide and Supportive treatment in people with Bronchiolitis, run by Beyond Air Inc. at 10 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 12 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 9 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Hospital Length of Stay (LOS) (time frame: 12 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 NCT03053388, 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 9 Jul 2019.