Bronchiolitis AcutePhase 4NCT03364218
Nebulized N-Acetyl Cysteine for Bronchiolitis in Inpatient Hospital Use
A Phase 4 study testing N-Acetyl Cysteine in people with Bronchiolitis Acute, run by Carilion Clinic at 1 site in United States.
Trial summary
Bronchiolitis is the major cause of hospital admission in infants < 6 months of age and usually viruses like Respiratory syncytial virus (RSV), human metapneumo virus, Adeno virus, para-influenza virus, Rhino virus and influenza virus are the main culprit. Read more about this study
- Who is it for?
- Ages 1 week to 2 years
- Conditions the study is for
- Bronchiolitis Acute
- What is being tested?
- N-Acetyl Cysteine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2018to 31 May 2020
- Phase
- Phase 4
- 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 week to 2 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Full term new born neonates up to patients < 2yrs
- Respiratory score ≥2
- Otherwise healthy with new respiratory illness
Who cannot join
- Prematurity <34 weeks for patients <6 months age.
- h/o congenital heart disease requiring baseline medication
- Patient received diagnosis of Asthma or reactive airway disease in past.
- Anatomic airway defect.
- Immunodeficiency
- Chronic lung disease
Show all 9Show fewer
- Patients who have had previous bronchiolitis < 4 weeks ago
- Patients intubated for acute bronchiolitis during the current admission.
- h/o Larynogomlacia, bronchomalacia or tracheomalacia.
Trial locations and contacts
1 site in 1 country.
Virginia Powel, MD contact
United States1 site, 1 recruiting
- Recruiting
Carilion Clinic
Roanoke, Virginia, 24014
Rahul Pandey, MD, 917-374-5746, rkpandey@carilionclinic.org
About this study
Official title: Nebulized N-Acetyl Cysteine for Bronchiolitis in Inpatient Hospital Use: A Randomized Controlled Trial
Bronchiolitis is the major cause of hospital admission in infants < 6 months of age and usually viruses like Respiratory syncytial virus (RSV), human metapneumo virus, Adeno virus, para-influenza virus, Rhino virus and influenza virus are the main culprit. In the US, acute bronchiolitis in infancy is responsible for approximately 150,000 hospitalizations yearly at an estimated cost of $500 million. Globally in 2005 it was estimated that at least 33.8 million were affected with RSV and in the same year, RSV associated severe acute lower respiratory infection (ALRI) were responsible for ~3.4 million hospitalizations and 66,000-199,000 deaths worldwide, with 99% of these deaths in developing countries.
In acute bronchiolitis there is cellular swelling and excessive mucus production. There is also proliferation of goblet cells, which leads to increased mucus production. The excess mucus produced is poorly cleared by non-ciliated (regenerating) epithelial cells leading to areas of narrowing and blocking of the bronchioles, causing the airway obstruction, hyperinflation, increased airway resistance, atelectasis and increased ventilation-perfusion mismatch that characterize acute bronchiolitis.
Read more
Currently there is no medicine that has proven effective in treating acute bronchiolitis and per American Academy of Pediatrics guidelines the management of acute bronchiolitis remains supportive care for the acute respiratory failure associated with acute bronchiolitis.
N-Acetyl Cysteine (NAC) is an antioxidant, anti-mucus compound that increases intracellular glutathione at the cellular level. It cleaves disulfide bonds by converting them to two sulfhydryl groups. This action results in the breakup of mucoproteins in lung mucus, reducing their chain lengths and thinning the mucus. Nebulized NAC is not studied well in acute bronchiolitis and is uncommonly used for the same. NAC has been studied in the treatment of various disease states, including those pulmonary in nature such as cystic fibrosis, chronic bronchitis, non-cystic fibrosis bronchiectasis and found to be beneficial.
With this background knowledge, the purpose of this study is to evaluate the effectiveness of nebulized mucolytic therapy in treatment of children with viral bronchiolitis.
Read the detailed description
A randomized clinical trial with blinding of person assigned for assessing and scoring the patients. The participants will include children less than 2 yrs. age admitted to the Pediatric Intensive Care Unit (PICU) with a diagnosis of acute bronchiolitis who will be randomized into either the NAC group or the non-NAC (Control) group.
Patients with acute bronchiolitis who require to be started on high flow nasal cannula support or any other noninvasive ventilator/BIPAP support are transferred/directly admitted to PICU. There is no time limit between when patients are admitted and when patients must sign consent or be randomized.
After a patient with acute bronchiolitis is identified, a member of the study team will perform a chart review to assess eligibility as described by the inclusion/exclusion criteria. If eligible, parent(s)/guardian(s) will be approached and Informed Consent will be obtained. Using randomization software(www.randomizer.org) the enrolled patients will be randomly assigned to either the NAC group or the non-NAC (Control) group.
The NAC will be ordered by the on call pharmacist and it will be administered by the on call Respiratory therapists. Between the two groups only the NAC group will get nebulized 2 ml of 10% NAC solution every 12 hours during their stay in PICU.
The PICU uses HHFNC (humidified high flow nasal canula), Heliox and non-invasive ventilation such as RAM canula, Neurally adjusted ventilatory assist (NAVA) and BIPAP. The PICU also typically uses Dexmedetomidine infusion once the patient is on non invasive ventilation (NIV) as a light sedation medication to avoid agitation and better ventilation patient synchrony.
The scoring tool used by Seattle children's Bronchiolitis pathway will be used. HHFNC (humidified high flow nasal cannula) will be started for patients when scores are ≥2. Depending on the clinical worsening the patient may require help with Heliox and escalation to non-invasive ventilation.
There will be twice a day blind assessments completed by experienced PICU/Transport nurses who were non-involved in patient care in PICU at that time. The pharmacist is going to use randomization software to randomly assign patients to a group (i.e control vs treatment). Also, the pharmacist will order code called as "Trial*" in the medical record (* denotes a number assigned) and depending on the randomization the patient may or may not get the trial medication (Nebulized NAC). As such, all patients in the study will have a medical record orders which look similar to help achieve blinding at this stage for the treating physicians and independent evaluators.
All patients in the study will receive a type of respiratory support, such as High flow nasal cannula, noninvasive ventilator/ BIPAP etc. and because the NAC neb can easily be given through those circuits, no extra equipment will be required for patients who are in the treatment (NAC) group. Given that there is no difference in equipment in both treatment and control groups, the only way the double-blind is broken in this scenario is NAC's odor.
The odor of Neb NAC typically stays in the room during the treatment (2-3 minutes) and should not last >30 minutes after every administration. NAC is a sulfur compound and hence smells like "rotten eggs" so for precaution to maintain blindness, a respiratory therapist will spray a commercial rotten egg smelling solution at approximately the same time as treatment is administered for all patients in the study.
Because the NAC neb will be delivered through a closed respiratory circuit and also because the respiratory therapists use filters for nebulization treatments, the chances of sticky residues will be lower and hence difficult to figure out by examination.
The 12 hourly neb treatments will occur from 6:30-7:30am and pm respectively. This timing works in favor for blinding because both attending physicians and the independent evaluators are less likely to be present during this time. The assessment will involve scoring the patients according to the bronchiolitis scoring data tool. These assessments will be completed for the duration of the PICU stay. The on service PICU attendings will only be involved in clinical management of patients and will be blinded from randomization. The blinding will be broken if one of the on service physicians or PICU/Transport nurses performing assessments are aware of the currently admitted patient randomization details.
Reasons subjects may be withdrawn from the study: patient gets transferred to another facility due to family's requests, family wishes to withdraw in the middle of the study, or to protect the welfare of the patient.
- Conditions
- Bronchiolitis Acute
- Being tested
- N-Acetyl Cysteine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-Acetyl CysteineDrug
Also called NAC
Nebulized N-Acetyl Cysteine administered every 12 hours
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Experimental | Subjects will receive N-Acetyl Cysteine (NAC) nebulized 2 mL of 10% NAC solution every 12 hours during their stay in the Pediatric Intensive Care Unit. Receives: Drug: N-Acetyl Cysteine |
| Control Group | No intervention | Subjects will not receive NAC, but will receive standard care for acute bronchiolitis. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Respiratory Score
4 item scoring system completed by clinician used to assess respiratory symptoms. Each item is scored 0-3, with the value increasing as severity of symptoms increases.
Measured: 1. Twice daily by physician 2. 15-30 min pre-treatment by nurse 3. 15-30 and 90 min post-treatment by nurse
Time on Non-Invasive Ventilation
Length of time on NIV
Measured: From time of PICU admission to time of PICU discharge, assessed up to 4 weeks
Duration of PICU/Hospital Admission
Length of time patient remains hospitalized
Measured: From time of hospital admission to time of hospital discharge, assessed up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2017
- Study start1 Feb 2018
- Primary completion31 May 2020 (estimated)
- Study completion31 May 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bronchiolitis AcuteStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 106 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Carilion Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rahul Pandey, Carilion Clinic
- Investigators
- Rahul Pandey, MD, Principal investigator, Carilion Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03364218
- Sponsor's protocol ID
- IRB# 2314
- Status last verified
- Sep 2019
- First submitted
- 30 Nov 2017
- Last updated
- 26 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nebulized N-Acetyl Cysteine for Bronchiolitis in Inpatient Hospital Use: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03364218
- Acronym / sponsor ID
- IRB# 2314
- Conditions
- Bronchiolitis Acute
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 106 participants (estimated)
- Lead sponsor
- Carilion ClinicUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 31 May 2020 (estimated)
- Study completion
- 31 May 2020 (estimated)
- First posted
- 6 Dec 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.
Bronchiolitis is the major cause of hospital admission in infants < 6 months of age and usually viruses like Respiratory syncytial virus (RSV), human metapneumo virus, Adeno virus, para-influenza virus, Rhino virus and influenza virus are the main culprit. In the US, acute bronchiolitis in infancy is responsible for approximately 150,000 hospitalizations yearly at an estimated cost of $500 million. Globally in 2005 it was estimated that at least 33.8 million were affected with RSV and in the same year, RSV associated severe acute lower respiratory infection (ALRI) were responsible for ~3.4 million hospitalizations and 66,000-199,000 deaths worldwide, with 99% of these deaths in developing countries.
In acute bronchiolitis there is cellular swelling and excessive mucus production. There is also proliferation of goblet cells, which leads to increased mucus production. The excess mucus produced is poorly cleared by non-ciliated (regenerating) epithelial cells leading to areas of narrowing and blocking of the bronchioles, causing the airway obstruction, hyperinflation, increased airway resistance, atelectasis and increased ventilation-perfusion mismatch that characterize acute bronchiolitis.
Currently there is no medicine that has proven effective in treating acute bronchiolitis and per American Academy of Pediatrics guidelines the management of acute bronchiolitis remains supportive care for the acute respiratory failure associated with acute bronchiolitis.
N-Acetyl Cysteine (NAC) is an antioxidant, anti-mucus compound that increases intracellular glutathione at the cellular level. It cleaves disulfide bonds by converting them to two sulfhydryl groups. This action results in the breakup of mucoproteins in lung mucus, reducing their chain lengths and thinning the mucus. Nebulized NAC is not studied well in acute bronchiolitis and is uncommonly used for the same. NAC has been studied in the treatment of various disease states, including those pulmonary in nature such as cystic fibrosis, chronic bronchitis, non-cystic fibrosis bronchiectasis and found to be beneficial.
With this background knowledge, the purpose of this study is to evaluate the effectiveness of nebulized mucolytic therapy in treatment of children with viral bronchiolitis.
Detailed description
A randomized clinical trial with blinding of person assigned for assessing and scoring the patients. The participants will include children less than 2 yrs. age admitted to the Pediatric Intensive Care Unit (PICU) with a diagnosis of acute bronchiolitis who will be randomized into either the NAC group or the non-NAC (Control) group.
Patients with acute bronchiolitis who require to be started on high flow nasal cannula support or any other noninvasive ventilator/BIPAP support are transferred/directly admitted to PICU. There is no time limit between when patients are admitted and when patients must sign consent or be randomized.
After a patient with acute bronchiolitis is identified, a member of the study team will perform a chart review to assess eligibility as described by the inclusion/exclusion criteria. If eligible, parent(s)/guardian(s) will be approached and Informed Consent will be obtained. Using randomization software(www.randomizer.org) the enrolled patients will be randomly assigned to either the NAC group or the non-NAC (Control) group.
The NAC will be ordered by the on call pharmacist and it will be administered by the on call Respiratory therapists. Between the two groups only the NAC group will get nebulized 2 ml of 10% NAC solution every 12 hours during their stay in PICU.
The PICU uses HHFNC (humidified high flow nasal canula), Heliox and non-invasive ventilation such as RAM canula, Neurally adjusted ventilatory assist (NAVA) and BIPAP. The PICU also typically uses Dexmedetomidine infusion once the patient is on non invasive ventilation (NIV) as a light sedation medication to avoid agitation and better ventilation patient synchrony.
The scoring tool used by Seattle children's Bronchiolitis pathway will be used. HHFNC (humidified high flow nasal cannula) will be started for patients when scores are ≥2. Depending on the clinical worsening the patient may require help with Heliox and escalation to non-invasive ventilation.
There will be twice a day blind assessments completed by experienced PICU/Transport nurses who were non-involved in patient care in PICU at that time. The pharmacist is going to use randomization software to randomly assign patients to a group (i.e control vs treatment). Also, the pharmacist will order code called as "Trial*" in the medical record (* denotes a number assigned) and depending on the randomization the patient may or may not get the trial medication (Nebulized NAC). As such, all patients in the study will have a medical record orders which look similar to help achieve blinding at this stage for the treating physicians and independent evaluators.
All patients in the study will receive a type of respiratory support, such as High flow nasal cannula, noninvasive ventilator/ BIPAP etc. and because the NAC neb can easily be given through those circuits, no extra equipment will be required for patients who are in the treatment (NAC) group. Given that there is no difference in equipment in both treatment and control groups, the only way the double-blind is broken in this scenario is NAC's odor.
The odor of Neb NAC typically stays in the room during the treatment (2-3 minutes) and should not last >30 minutes after every administration. NAC is a sulfur compound and hence smells like "rotten eggs" so for precaution to maintain blindness, a respiratory therapist will spray a commercial rotten egg smelling solution at approximately the same time as treatment is administered for all patients in the study.
Because the NAC neb will be delivered through a closed respiratory circuit and also because the respiratory therapists use filters for nebulization treatments, the chances of sticky residues will be lower and hence difficult to figure out by examination.
The 12 hourly neb treatments will occur from 6:30-7:30am and pm respectively. This timing works in favor for blinding because both attending physicians and the independent evaluators are less likely to be present during this time. The assessment will involve scoring the patients according to the bronchiolitis scoring data tool. These assessments will be completed for the duration of the PICU stay. The on service PICU attendings will only be involved in clinical management of patients and will be blinded from randomization. The blinding will be broken if one of the on service physicians or PICU/Transport nurses performing assessments are aware of the currently admitted patient randomization details.
Reasons subjects may be withdrawn from the study: patient gets transferred to another facility due to family's requests, family wishes to withdraw in the middle of the study, or to protect the welfare of the patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | Experimental | Drug: N-Acetyl CysteineSubjects will receive N-Acetyl Cysteine (NAC) nebulized 2 mL of 10% NAC solution every 12 hours during their stay in the Pediatric Intensive Care Unit. |
| Control Group | No intervention | –Subjects will not receive NAC, but will receive standard care for acute bronchiolitis. |
Who may qualify
- Ages
- 1 week to 2 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Full term new born neonates up to patients < 2yrs
- Respiratory score ≥2
- Otherwise healthy with new respiratory illness
Key exclusion criteria (9 listed)
- Prematurity <34 weeks for patients <6 months age.
- h/o congenital heart disease requiring baseline medication
- Patient received diagnosis of Asthma or reactive airway disease in past.
- Anatomic airway defect.
- Immunodeficiency
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 |
|---|---|---|
| N-Acetyl CysteineAlso: NACNebulized N-Acetyl Cysteine administered every 12 hours | Drug | Treatment Group |
Primary outcome
Respiratory Score
Time frame: 1. Twice daily by physician 2. 15-30 min pre-treatment by nurse 3. 15-30 and 90 min post-treatment by nurse
4 item scoring system completed by clinician used to assess respiratory symptoms. Each item is scored 0-3, with the value increasing as severity of symptoms increases.
Time on Non-Invasive Ventilation
Time frame: From time of PICU admission to time of PICU discharge, assessed up to 4 weeks
Length of time on NIV
Duration of PICU/Hospital Admission
Time frame: From time of hospital admission to time of hospital discharge, assessed up to 4 weeks
Length of time patient remains hospitalized
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2019.
- Individual participant dataSharing planned: No
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GVHD (Acute or Chronic)
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.
Virginia Powel, MD contact
Rahul Pandey, MD principal investigator
Carilion Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing N-Acetyl Cysteine in people with Bronchiolitis Acute, run by Carilion Clinic 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 9 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: status not confirmed, as of the sponsor's last update on 26 Sep 2019. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rahul Pandey, MD (9173745746, rkpandey@carilionclinic.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Respiratory Score (time frame: 1. Twice daily by physician 2. 15-30 min pre-treatment by nurse 3. 15-30 and 90 min post-treatment by nurse). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Sep 2019.