Contact information
Type
Scientific
Primary contact
Dr Sherri Katz
ORCID ID
Contact details
Children's Hospital of Eastern Ontario
401 Smyth Road
w1406
Ottawa
K1H 8L1
Canada
+1 613 737 7600 ext. 2868
skatz@cheo.on.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
In-ex TREND study
Study hypothesis
We will be looking specifically at a heterogeneous group of neuromuscular disorders which, either as a secondary consequence of degeneration of the spinal nerves (spinal muscular atrophy, amyotrophic lateral sclerosis) or as a primary muscle defect (muscular dystrophies, myopathies) result in progressive loss of muscle strength. Respiratory complications are the primary cause of morbidity and mortality associated with these diseases, as involvement of the respiratory muscles leads to either progressive hypoventilation or recurrent atelectasis and pneumonia secondary to decreased cough efficacy.
For this study we will look at those children with neuromuscular disorders who are admitted to hospital with a respiratory deterioration (hypoxemia and/or the presence of new onset radiologically proven atelectasis or consolidation).
Hypotheses:
We expect that the addition of the Emerson in-exsufflator to a standard treatment regimen for acute respiratory deterioration:
1. Will result in a decreased duration of hospitalisation in a population of children with neuromuscular disease
2. Resulting in hospitalisation will decrease the time requiring supplemental oxygen in a population of children with neuromuscular disease
3. Resulting in hospitalisation will result in a more rapid improvement in chest X-ray changes in a population of children with neuromuscular disease
4. Resulting in hospitalisation will decrease the length of stay in intensive care unit or days invasively ventilated in a population of children with neuromuscular disease
Ethics approval
Each site will submit to their local hospital ethics boards. Ethics approval received from the Children's Hospital of Eastern Ontario Research Ethics Board (REB) on the 2nd October 2007 (ref: 07/24E).
Study design
Multi-centre randomised unblinded controlled trial of the mechanical inexsufflator. Randomisation sequence will be stratified by centre with a block-size randomisation protocol.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Children with neuromuscular disorders who are admitted to hospital with a respiratory deterioration (hypoxemia and/or the presence of new onset radiologically proven atelectasis or consolidation).
Intervention
1. Conventional treatments, as deemed appropriate by the treating physician:
1.1. Physiotherapy
1.2. Nutritional support
1.3. Antibiotics (fever, elevated White Blood Cells [WBC])
1.4. Non-invasive positive pressure ventilation
2. Conventional treatments and Emerson in-exsufflator
Using Friedman's formula for survival analysis study design, 62 patients per arm would achieve 80% power to detect a hazard ratio of 1.4. To account for potential withdrawals and withdrawal of consent, estimated at about 2.5%, four additional participants will be recruited for a grand total of 128 participants.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
Time to discharge: an estimate of the primary end-point, time to discharge with standard care, was based on the clinical experience of the principal investigators and is currently being verified with a three-year retrospective chart review at Childrens Hospital of Eastern Ontario (CHEO). The mean length of stay in these patients is estimated to be 10 days. Discussions with several paediatric respirologists have taken place, focusing on what magnitude of difference in time to discharge would be clinically important between treatment and control groups. The consensus was a Minimally Clinically Important Difference (MCID) of three days' reduction from the average current length of stay in the study population. These numbers translate to a hazard ratio of 1.4. A two-sided time-to-event test at a = 0.05 will be used to detect a significant difference in time to discharge between the two arms.
Secondary outcome measures
1. Time (in days) to improvement in oxygenation (no longer requiring supplemental oxygen for 24 hours)
2. X-ray changes: improvement or progression (increasing atelectasis, consolidation)
3. Development of acute hypercapnic respiratory failure requiring intubation and mechanical ventilation
4. Days in intensive care unit
Overall trial start date
01/10/2007
Overall trial end date
01/04/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients aged 3 to 17 years
2. Patients have a known neuromotor disorder affecting respiratory muscles
3. Admitted to hospital with a respiratory deterioration (hypoxemia in the presence of new onset radiologically proven atelectasis or consolidation)
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
128
Participant exclusion criteria
1. Refusal to participate
2. Already using the Emerson in-exsufflator at home on a regular basis
3. Development of new uncompensated hypercapnic respiratory failure requiring intubation and mechanical ventilation
4. History of bullous emphysema, known susceptibility to pneumothorax or pneumomediastinum, or known to have had any recent barotraumas
Recruitment start date
01/10/2007
Recruitment end date
01/04/2009
Locations
Countries of recruitment
Canada
Trial participating centre
Children's Hospital of Eastern Ontario
Ottawa
K1H 8L1
Canada
Sponsor information
Organisation
Children's Hospital of Eastern Ontario (Canada)
Sponsor details
c/o Sherri Katz
MD
401 Smyth Road
W1406
Ottawa
K1H 8L1
Canada
+1 613 737 7600 ext. 2868
skatz@cheo.on.ca
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Fight Spinal Muscular Atrophy (FightSMA) (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list