Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04737655 |
| Other study ID # |
B7072020000051 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
February 15, 2021 |
| Est. completion date |
May 15, 2023 |
Study information
| Verified date |
February 2021 |
| Source |
University of Liege |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Objective: To evaluate non-inferiority of Trimbow, an approved therapy for treatment of
severe COPD, in ICU compared to the standard of care which is based on the same therapeutic
approach.
Study location: CHU Sart-Tilman, 4000 Liège, Belgium Study duration: 2 years
Type : Interventional
Methodology: Prospective clinical trial Number of patients: 200 (randomized 1:1)
Main Inclusion criteria :
- Maintenance therapy (LAMA or LABA) for COPD
- Age >18
- Admission for AE of COPD
- Signed Inform consent
- Admitted in ICU >24h
Description:
In the ICU, the standard of care is still focused on the use of aerosolized therapies. These
therapies are time consuming and largely used unless the lack of proven superiority in
comparison with Pressurised metered dose inhalers (pMDIs) which are as effective and easier
to use. Moreover, aerosolized therapies are associated with an increased risk of
oropharyngeal deposition and not always efficiently delivered.
The use of new ventilation techniques like high flow canula oxygen therapy is also
challenging in the particular context of inhaled therapies. Nowadays, no data are available
to confirm the appropriate deposition of the inhaled therapies. Therefore, it's necessary to
have to move forward the evaluation of pMDIs in the particular context of non invasive
ventilation (for example with high-flow nasal oxygen therapy).
As the use of triple therapy is now the standard of care in COPD patients experiencing a
severe exacerbation, it is the objective to propose the introduction of Trimbow as soon as
possible following the onset of a severe exacerbation, even in critically ill patients.
3 Study objectives
3.1 Main objective
Evaluate the non inferiority of Trimbow associated with the standard of care in comparison
with the standard of care alone.
3.2 Secondary objectives
Evaluate the other ICU-stay outcomes and long term outcomes of the patients.
4 Type of Study
An open label, prospective randomized trial
Phase A : Open label, prospective study in hospital. Shift in phase IV at hospital discharge
(reimbursed treatment in Belgium, use of Trimbow as recommended)
Phase B : Trimbow prescribed as accepted in Belgium following reimbursement criteria :
observational study (12 months), out of hospital. One visit in hospital every 3 months (as
usual) with classical evaluation during the visit (clinical, functional, symptomatic, scales,
exacerbation) 5 Study population
The study population will consist of one cohort of patients admitted in our hospital (CHU DE
LIEGE) for acute exacerbation of COPD. The COPD has to be diagnosed based on the
international recommendations (GOLD recommendations). The patient has to suffer from an acute
severe exacerbation requiring an ICU stay of at least 24hours.
Patients will be separated in 2 randomized groups (Trimbow + SOC versus SOC) 1:1.
A total of 200 patients will be randomized in this study following the inclusion and
exclusions criteria.
The study will be spited in 2 phases:
- Phase A: Hospitalization (interventional)
- Phase B: Follow up study after discharged (observational)
Investigational therapy TRIMBOW® pressurised inhalation solution: Beclometasone dipropionate
/ formoterol fumarate /glycopyrronium 87/5/9 µg per inhalation
Reference therapy DUOVENT®: Fenoterol 50 microg/ipratropium 20 microg (400/160 per day to
800/320 per day) Plus FLIXOTIDE®: fluticasone propionate (250-100 microg/day)
Administration Informed consent: our study falls within the context of the law governing
clinical studies and requires the signature of an informed consent which will be duly signed
with the presence of an investigator and after the patient or his legal representative has
been able to ask the set of his questions.
Practical aspects At admission in our hospital, the patient or its legal representative will
be asked to participate in the TRIMICU study. All the explanations will be given by the data
manager in charge of the study. After a period of reflection, a local investigator will
re-consider the different aspects of the study with the various stakeholders and will
personally supervise the signing of the informed consent.
After signature, the patient will be randomized to trimbow + SOC versus SOC alone. Patients
will be randomized in groups of 20 patients 10/10 by the study director or the data nurse.
None of them will have any therapeutic contact with patients.
Once started, the patient will be followed daily by the data manager during his
hospitalization (via study of the computerized file) and once every 3 months after his
discharge from hospitalization by telephone contact and a follow-visit every 3 months.
Phase A:
Composite primary endpoint At ICU discharge: non inferiority of Trimbow + SOC versus SOC
alone
- ICU Length of stay
- Time of Ventilation
At hospital discharge
- In hospital length of stay
Phase B Explore the survival rate without exacerbation at 1 year.
Safety variables Trimbow is known to be efficient in the specific case of severe COPD which
is by definition the case of all COPD patients admitted in ICU. As it is the standard of care
per se for ambulatory patients, treating patients earlier with this specific therapy designed
for COPD patients is theoretically appropriate. Trimbow is compound of bronchodilators and
inhaled corticosteroids already used in the specific ICU onset. No safety issue is expected
for this specific study.
Safety variables
- Pneumonia
- Time of mechanical ventilation
- Need for invasive mechanical ventilation
- Ventilator-acquired pneumonia (VAP)
- Tachyarythmia
- Myocardial infarction
Statistical analysis Two primary endpoints were considered for the sample size determination:
(1) the length of hospitalization stay (days) during Phase I, and (2) the survival rate (%)
without exacerbation at 1 year during Phase II. It was found that a total of 200 patients
(including a 15% drop-out rate) randomized in two groups of 100 subjects would be necessary
to show the non-inferiority of the "SOC+Trimbow" treatment compared to "SOC alone" treatment
with a power of 80% and an overall significance level of 5% for the two outcomes, by using
two one-sided unpaired t-test at α=0.025. In the power calculation, a non-inferiority margin
of 2 days was assumed for the hospitalization length of stay and of 5% for the survival
without exacerbation at 1 year.
Statistical Methods Descriptive statistics will be performed for each continuous variable
measured and will include mean, median, standard deviation, minimum, maximum and number of
available observation. Frequency distributions will be used for ordinal and nominal variables
and will include numbers and percentages of each of the scores or categories, and the number
of missing observations.
All variables will be compared between control group (SOC alone) and test group (SOC +
Trimbow) with the convenient statistical test. The primary outcomes i.e. survival without
exacerbation at 1 year and length of hospitalization stay, will be compared with a
non-inferiority test.
Statistics will be done on the maximum available data. Results will be considered significant
at the 5% level (p<0.05). Calculations will be done with SAS version 9.4 and R.
Data anonymization and Security Each subject in the study will be assigned a unique subject
number and will keep that number throughout the study. The medical investigators will keep a
list linking the subject's number to the subject's names. He will follow all applicable
privacy laws in order to protect a subject's privacy and confidentiality.
