FreeDom Strategy for COPD Exacerbations

Overseen By François Lellouche

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Laval University

Disqualifiers: Sleep apnea, NIV at home, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The main objective of the study is to assess the "FreeDom" innovative strategy (FreeO2 at Domicile) to reduce hospitalization duration in patients with COPD exacerbation. This strategy associates early hospital discharge, automated O2 flow weaning with FreeO2 system, telemedicine and tele-rehabilitation. The main hypothesis of this study is that the FreeDom strategy will reduce the number of hospitalization day by 50 percent at day 30.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the FreeDom treatment for COPD exacerbations?

The research highlights the importance of placebo-controlled trials in determining the effectiveness of treatments for COPD. Although specific data on the FreeDom treatment is not provided, the studies emphasize the need for strong evidence showing a treatment's superiority over placebo before considering it effective. ^{1 2 3 4 5}

Is the FreeDom Strategy for COPD Exacerbations safe for humans?

The available research does not provide specific safety data for the FreeDom Strategy for COPD Exacerbations, but it does mention that serious adverse events, including pneumonia, were more frequent in a related study. This suggests that while the treatment may be safe for some, there could be risks involved, and it's important to discuss these with a healthcare provider. ^{4 6 7 8 9}

How does the Control treatment for COPD exacerbations differ from other treatments?

The Control treatment, which involves a placebo or standard care, is unique because it serves as a baseline to compare the effectiveness of other treatments in clinical trials, rather than providing a direct therapeutic effect itself. ^{2 4 10 11 12}

Research Team

François Lellouche

Principal Investigator

Laval University

Eligibility Criteria

This trial is for COPD patients needing moderate oxygen therapy (<6L/min) to maintain SpO2 > 90%, hospitalized for less than 48 hours, aged over 40 with a history of smoking. It's not for those non-autonomous and alone at home, refusing consent, needing imminent intubation, with sleep apnea or living far from the hospital (>50 km).

Inclusion Criteria

I need less than 6L/min of oxygen to keep my oxygen levels above 90%.

I am 40 years old or older.

I was hospitalized for a severe COPD flare-up but stayed less than 48 hours.

Exclusion Criteria

Patient already included in the study within 3 months

A lung doctor thinks that you will need a breathing tube very soon.

I need help with daily activities and live alone.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Initial Hospitalization

Participants undergo initial conventional hospitalization with automated O2 flow rate titration by FreeO2 system

Up to 30 days

Home Hospitalization

Participants receive home hospitalization with automated oxygen flow titration, telemedicine, and tele-rehabilitation

Approximately 1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including consultations and quality of life assessments

3 months

Treatment Details

Interventions

• Control
• FreeDom

Trial Overview The 'FreeDom' strategy is being tested to cut hospital stays by half in COPD exacerbation cases. It includes early discharge, automated O2 weaning using FreeO2 system, telemedicine and tele-rehabilitation.

Participant Groups

Group I: Control Experimental Treatment 1 Intervention

The intervention is an hospitalization with usual care. The hospitalization will take place in the usual setting and the hospital discharge will be decided by pulmonologists according to the usual criteria

Group II: FreeDom Active Control 1 Intervention

FreeDom strategy (early discharge, automated weaning at home, telemedicine, telereadaptation): -initial conventional hospitalization before discharge home, O2 flow rate automatically titrated by FreeO2 (based on a SpO2 target). The hospital discharge will be possible if the definite criteria are met. After hospital discharge, patient will have home hospitalisation. Automated oxygen flow titration, patient education will be conducted for using the telemedicine system, for questionnaires and for the tele-rehabilitation program will be initiated for home hospitalization,

Who Is Running the Clinical Trial?

Laval University

Lead Sponsor

Trials

439

Recruited

178,000+

Findings from Research

The meta-analysis of asthma drug therapy trials revealed a small but measurable placebo effect in stable asthmatic patients, with a mean increase in forced expiratory volume in 1 second (FEV1) of 0.11 L/min and a 4.81% increase, indicating that some patients may experience improvements even without active treatment.

Interestingly, while the placebo group showed a slight increase in FEV1, they experienced a decrease in peak expiratory flow (PEF) by 2.24 L/min, suggesting that different measures of lung function can respond differently to placebo, highlighting the complexity of asthma treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in asthma drug therapy trials: a meta-analysis. Joyce, DP., Jackevicius, C., Chapman, KR., et al.[2019]

In a study involving 281 COPD patients, fluticasone propionate significantly reduced the severity of exacerbations compared to placebo, with 60% of patients experiencing moderate or severe exacerbations versus 86% in the placebo group (p<0.001).

Patients treated with fluticasone propionate showed significant improvements in lung function and symptoms, including increased peak expiratory flow and a greater 6-minute walking distance, while the treatment was well-tolerated with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group. Paggiaro, PL., Dahle, R., Bakran, I., et al.[2022]

A systematic review of 100 trials involving 34,029 patients found that placebo-controlled trials have not provided convincing evidence that antibiotics are effective for treating mild to moderate exacerbations of chronic obstructive pulmonary disease (COPD).

The inconclusive results from placebo-controlled trials raise ethical concerns about conducting head-to-head trials comparing different antibiotics, as they may not be justified without clear evidence of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Where is the supporting evidence for treating mild to moderate chronic obstructive pulmonary disease exacerbations with antibiotics? A systematic review. Puhan, MA., Vollenweider, D., Steurer, J., et al.[2018]

In the UPLIFT trial, patients assigned to the placebo group had a significantly higher rate of premature discontinuation (45%) compared to those receiving tiotropium (37%), indicating that treatment assignment impacts trial completion rates.

Patients who discontinued were generally more severe in their COPD symptoms, had worse lung function (lower FEV1), and poorer health-related quality of life, suggesting that these factors contribute to higher dropout rates in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Premature discontinuation during the UPLIFT study. Decramer, M., Molenberghs, G., Liu, D., et al.[2015]

In a study involving 53 patients with chronic obstructive pulmonary disease (COPD), regular use of short-acting inhaled beta-agonists like albuterol did not provide any significant physiological or clinical benefits compared to using them as needed.

Despite patients using twice as much albuterol during the regular treatment period, there were no meaningful differences in lung function or quality of life measures, indicating that regular beta-agonist therapy may not be beneficial for COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease. Cook, D., Guyatt, G., Wong, E., et al.[2013]

The Salford Lung Study (SLS) revealed that patients with COPD in real-world settings are older, have more comorbidities, and experience more frequent exacerbations compared to those in traditional efficacy trials, highlighting a gap in representativeness.

Only about 30% of SLS patients would qualify for inclusion in standard efficacy trials, suggesting that results from these trials may not fully apply to the broader COPD population seen in everyday clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness versus efficacy trials in COPD: how study design influences outcomes and applicability. Woodcock, A., Boucot, I., Leather, DA., et al.[2022]

In a pooled analysis of four studies involving 1232 adults with COPD, 80.1% of patients demonstrated correct use of the placebo ELLIPTA dry-powder inhaler, indicating a high level of adherence to the inhaler technique guidelines.

Additionally, 95.7% of patients found the ELLIPTA DPI easy or very easy to use, suggesting that the design of the inhaler may facilitate better patient compliance and management of COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correct use and ease-of-use of placebo ELLIPTA dry-powder inhaler in adult patients with chronic obstructive pulmonary disease. Siler, TM., Jain, R., Collison, K., et al.[2022]

In a study involving 16,417 patients with moderate COPD, prior treatment with inhaled corticosteroids and bronchodilators was associated with improved mortality outcomes when treated with fluticasone furoate and vilanterol compared to placebo, suggesting that previous medication use can enhance treatment efficacy.

However, prior treatment did not show a consistent impact on the frequency of exacerbations during the study, indicating that while it may influence survival rates, it does not necessarily affect the occurrence of COPD flare-ups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of pre-enrolment medication use on clinical outcomes in SUMMIT. Vestbo, J., Dransfield, M., Anderson, JA., et al.[2020]

A systematic review of 56 randomized controlled trials involving 14,166 COPD patients indicated a trend of decreasing mortality rates, with an annual decrease of 6.1%, suggesting improvements in patient outcomes over the last two decades.

Although there is a positive correlation between exacerbation rates and mortality rates, the relationship is weak and insignificant, highlighting the need for careful trial design when comparing results across different studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COPD mortality and exacerbations in the placebo group of clinical trials over two decades: a systematic review and meta-regression. Andreas, S., Röver, C., Heinz, J., et al.[2022]

In a study of 102 adults with airflow obstruction, significant changes in lung function after placebo administration were established, with specific thresholds for FEV1, FVC, SVC, and IC that indicate meaningful responses.

The study found that inspiratory capacity (IC) showed the most variability, with changes greater than 0.30 L or 15% from baseline considered significant, while FEV1 and FVC changes above 0.20 L or 7% from baseline were also significant, providing important benchmarks for assessing lung function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spirometric changes in obstructive disease: after all, how much is significant? Soares, AL., Pereira, CA., Rodrigues, SC.[2022]

In a real-world study of 34,808 COPD patients, single-inhaler triple therapy did not show a significant advantage over dual bronchodilators in reducing exacerbations, except for patients with a history of multiple exacerbations.

However, patients using single-inhaler triple therapy experienced a higher risk of severe pneumonia, indicating that while it may be beneficial for some, dual bronchodilators could be a safer option for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Inhaler Triple versus Dual Bronchodilator Therapy in COPD: Real-World Comparative Effectiveness and Safety. Suissa, S., Dell'Aniello, S., Ernst, P.[2022]

In a study involving 175 patients with acute exacerbations of COPD, treatment with oral prednisone did not show a significant reduction in overall treatment failure compared to placebo, with a failure rate of 42.0% in the prednisone group versus 34.5% in the placebo group.

However, the study found that the respiratory-related treatment failure rate was significantly higher in the prednisone group (27.6%) compared to the placebo group (13.6%), suggesting that prednisone may not be effective in preventing complications related to respiratory issues in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral corticosteroids to treat outpatients with acute exacerbations of COPD in primary care: a multicentre pragmatic randomised controlled study. Thebault, JL., Roche, N., Abdoul, H., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

The placebo effect in asthma drug therapy trials: a meta-analysis. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Where is the supporting evidence for treating mild to moderate chronic obstructive pulmonary disease exacerbations with antibiotics? A systematic review. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Premature discontinuation during the UPLIFT study. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Effectiveness versus efficacy trials in COPD: how study design influences outcomes and applicability. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Correct use and ease-of-use of placebo ELLIPTA dry-powder inhaler in adult patients with chronic obstructive pulmonary disease. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Impact of pre-enrolment medication use on clinical outcomes in SUMMIT. [2020]

9. England pubmed.ncbi.nlm.nih.gov

COPD mortality and exacerbations in the placebo group of clinical trials over two decades: a systematic review and meta-regression. [2022]

10. Brazil pubmed.ncbi.nlm.nih.gov

Spirometric changes in obstructive disease: after all, how much is significant? [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Single-Inhaler Triple versus Dual Bronchodilator Therapy in COPD: Real-World Comparative Effectiveness and Safety. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral corticosteroids to treat outpatients with acute exacerbations of COPD in primary care: a multicentre pragmatic randomised controlled study. [2023]