Non-invasive Ventilation vs. Standard Therapy for Children Hospitalized With an Acute Exacerbation of Asthma

NCT ID: NCT03296579

Last Updated: 2018-05-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-30

Study Completion Date

2018-12-31

Brief Summary

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Acute asthma produces greatly increased work of breathing and increased oxygen requirement secondary to bronchial narrowing and airway obstruction by inflammatory secretions. There is growing evidence that non-invasive ventilation can reverse these processes more efficiently than conventional asthma therapy. Surprisingly, there have not yet been any large scale prospective controlled studies to investigate this hypothesis, (either in adults or children). Consequently, the aim of this study is to determine if the use of non-invasive positive airway pressure, for children admitted to hospital with an acute exacerbation of asthma, reduces their work of breathing, need for adjunctive medications, and shortens the length of hospital stay, compared to current standard therapy.

Detailed Description

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The aim of the study is to determine if the use of NIV, for children admitted to hospital with an acute exacerbation of asthma, reduces their work of breathing, need for adjunctive medication, length of hospital stay, and need for intubation and mechanical ventilation. Study design will be prospective, randomized and controlled. The tightly fitting face mask necessary for NIV makes it impossible to make this a blinded study.

The principal enrollment criteria will be children over 2 years of age presenting to the ER with acute asthma. After diagnosis, all children are treated with standard therapy (systemic steroids plus 3 doses of inhaled salbutamol and 1 dose of inhaled ipratropium over a 1 hour period then hourly salbutamol). The principal decision between discharge track and admission track will be made at 2 hours after first steroid dose. Admission criteria are based on sequential PRAM scores.

After initial asthma treatment and observation in the emergency room, to determine which patients can be discharged home, those who need admission will be asked to join the study, then consented and randomized. There will be three treatment groups:

* BiPAP: standard steroid dose, hourly salbutamol and BiPAP at 15/5 cm H2O by face mask with rate 10 to 15/min, oxygen as needed.
* CPAP: standard steroid dose, hourly salbutamol and 8 to 10 cm H2O constant pressure by face mask, oxygen as needed.
* Conventional therapy: standard steroid dose plus hourly nebulized salbutamol, nebulized ipratropium q 6 hrly, magnesium sulphate 50 mg/kg IV (4 doses q 6 hrly), loading dose of aminophylline 6 mg/kg IV if no progress, oxygen as needed.

All children will be admitted to a small 3 bed respiratory unit. They will be closely monitored and objectively scored every 4 hours using the PRAM asthma clinical severity score (Pediatric Respiratory Assessment Measure). Projected patient enrollment will be at least 30 in each arm. Estimated study duration is 6 months.

Conditions

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Asthma Acute Asthma in Children

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

It is not possible to use non-invasive face masks on the control patients so the study is unblinded.

Study Groups

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Conventional asthma therapy.

Bilevel Positive Airway Pressure group(BiPAP). BiPAP settings at 15/5 cm H2O by face mask with background rate 10 to 15/min. Standard steroid dose plus hourly salbutamol and oxygen to keep SaO2 \> 92%.

Group Type ACTIVE_COMPARATOR

Ipratropium

Intervention Type DRUG

Nebulized q6h

Magnesium Sulfate

Intervention Type DRUG

50mg/kg IV, 4 doses q6h

Aminophylline

Intervention Type DRUG

6mg/kg IV (if no progress)

Standard steroid dose, hourly salbutamol, oxygen as needed

Intervention Type DRUG

Standard common therapies for all three arms.

Non-invasive ventilation (CPAP).

Continuous Positive Airway Pressure group (CPAP). CPAP settings at 8 to 10 cm H2O. Standard steroid dose plus hourly salbutamol and oxygen to keep SaO2 \> 92%.

Group Type EXPERIMENTAL

CPAP

Intervention Type DEVICE

The patient breathes against a constant pressure delivered by face mask.

Standard steroid dose, hourly salbutamol, oxygen as needed

Intervention Type DRUG

Standard common therapies for all three arms.

Non-invasive ventilation (BiPAP)

Standard steroid dose, hourly salbutamol, oxygen as needed, nebulized ipratropium q 6 hrly, magnesium sulfate 50 mg/kg IV (4 doses q 6 hrly), loading dose of aminophylline 6 mg/kg IV if no progress.

Group Type EXPERIMENTAL

BiPAP

Intervention Type DEVICE

The patient's breathing is assisted by cycling between high and low pressures at a pre-set rate.

Standard steroid dose, hourly salbutamol, oxygen as needed

Intervention Type DRUG

Standard common therapies for all three arms.

Interventions

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BiPAP

The patient's breathing is assisted by cycling between high and low pressures at a pre-set rate.

Intervention Type DEVICE

CPAP

The patient breathes against a constant pressure delivered by face mask.

Intervention Type DEVICE

Ipratropium

Nebulized q6h

Intervention Type DRUG

Magnesium Sulfate

50mg/kg IV, 4 doses q6h

Intervention Type DRUG

Aminophylline

6mg/kg IV (if no progress)

Intervention Type DRUG

Standard steroid dose, hourly salbutamol, oxygen as needed

Standard common therapies for all three arms.

Intervention Type DRUG

Other Intervention Names

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Trilogy BiPAP Bilevel Positive Airway Pressure Continuous Positive Airway Pressure

Eligibility Criteria

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Inclusion Criteria

* 2-18 years old
* Clinical diagnosis of acute asthma exacerbation (respiratory rate greater than WHO's age-dependent criteria, a history of similar previous episodes and wheezing heard on auscultation by an experienced physician)
* PRAM score of 8 or more after 2 hours post-steroid administration
* Parents willing and able to sign consent
* Children over the age of 6 willing to provide assent

Exclusion Criteria

* Clinical suspicion of bacterial pneumonia: focal crackles or bronchial breathing, and/or major chest x-ray findings.
* Impending respiratory failure at presentation requiring direct PICU admission
* Any contraindication to BiPAP use including altered mental status, recent bowel surgery, intractable vomiting, inability to protect airway, pneumothorax.
* Receiving maintenance dose of oral steroid at time of hospital admission
* History of serious unrelated illness such as congenital heart disease or bronchopulmonary dysplasia.
Minimum Eligible Age

2 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role collaborator

University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Michael Seear

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael Seear

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Central Contacts

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Michael Seear, MD

Role: CONTACT

6048752000

Terry Viczko

Role: CONTACT

6048752345 ext. 5419

References

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Gowraiah V, Awasthi S, Kapoor R, Sahana D, Venkatesh P, Gangadhar B, Awasthi A, Verma A, Pai N, Seear M. Can we distinguish pneumonia from wheezy diseases in tachypnoeic children under low-resource conditions? A prospective observational study in four Indian hospitals. Arch Dis Child. 2014 Oct;99(10):899-906. doi: 10.1136/archdischild-2013-305740. Epub 2014 Jun 12.

Reference Type BACKGROUND
PMID: 24925892 (View on PubMed)

Basnet S, Mander G, Andoh J, Klaska H, Verhulst S, Koirala J. Safety, efficacy, and tolerability of early initiation of noninvasive positive pressure ventilation in pediatric patients admitted with status asthmaticus: a pilot study. Pediatr Crit Care Med. 2012 Jul;13(4):393-8. doi: 10.1097/PCC.0b013e318238b07a.

Reference Type BACKGROUND
PMID: 22067982 (View on PubMed)

Ducharme FM, Chalut D, Plotnick L, Savdie C, Kudirka D, Zhang X, Meng L, McGillivray D. The Pediatric Respiratory Assessment Measure: a valid clinical score for assessing acute asthma severity from toddlers to teenagers. J Pediatr. 2008 Apr;152(4):476-80, 480.e1. doi: 10.1016/j.jpeds.2007.08.034. Epub 2007 Oct 31.

Reference Type BACKGROUND
PMID: 18346499 (View on PubMed)

Martinez FD, Vercelli D. Asthma. Lancet. 2013 Oct 19;382(9901):1360-72. doi: 10.1016/S0140-6736(13)61536-6. Epub 2013 Sep 13.

Reference Type BACKGROUND
PMID: 24041942 (View on PubMed)

Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet. 2009 Jul 18;374(9685):250-9. doi: 10.1016/S0140-6736(09)60496-7.

Reference Type BACKGROUND
PMID: 19616722 (View on PubMed)

British Thoracic Society Standards of Care Committee. Non-invasive ventilation in acute respiratory failure. Thorax. 2002 Mar;57(3):192-211. doi: 10.1136/thorax.57.3.192. No abstract available.

Reference Type BACKGROUND
PMID: 11867822 (View on PubMed)

Nievas IF, Anand KJ. Severe acute asthma exacerbation in children: a stepwise approach for escalating therapy in a pediatric intensive care unit. J Pediatr Pharmacol Ther. 2013 Apr;18(2):88-104. doi: 10.5863/1551-6776-18.2.88.

Reference Type BACKGROUND
PMID: 23798903 (View on PubMed)

Papiris SA, Manali ED, Kolilekas L, Triantafillidou C, Tsangaris I. Acute severe asthma: new approaches to assessment and treatment. Drugs. 2009;69(17):2363-91. doi: 10.2165/11319930-000000000-00000.

Reference Type BACKGROUND
PMID: 19911854 (View on PubMed)

Green E, Jain P, Bernoth M. Noninvasive ventilation for acute exacerbations of asthma: A systematic review of the literature. Aust Crit Care. 2017 Nov;30(6):289-297. doi: 10.1016/j.aucc.2017.01.003. Epub 2017 Jan 27.

Reference Type BACKGROUND
PMID: 28139368 (View on PubMed)

Soroksky A, Klinowski E, Ilgyev E, Mizrachi A, Miller A, Ben Yehuda TM, Shpirer I, Leonov Y. Noninvasive positive pressure ventilation in acute asthmatic attack. Eur Respir Rev. 2010 Mar;19(115):39-45. doi: 10.1183/09059180.00006109.

Reference Type BACKGROUND
PMID: 20956164 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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H17-02008

Identifier Type: -

Identifier Source: org_study_id

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