Clinical trial NCT03890224: Respiratory Support in Chronic Obstructive Pulmonary Disease (COPD) Patients
Official title: Respiratory Support in Chronic Obstructive Pulmonary Disease (COPD) Patients After Acute Exacerbation With Monitoring the Quality of Support
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
COPD Exacerbation
Keywords: Respiratory Support
Lead sponsor: Clinact
Sponsor class: OTHER
Collaborators: name: Assistance Publique - Hôpitaux de Paris
name: Fondation du Souffle
First posted: 2019-03-26
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Rescue2-monitor is an open-label, prospective randomized, controlled, superiority clinical trial, performed in patients with hypercapnic chronic obstructive pulmonary disease post-acute hypercapnic exacerbation. Four arms (distributed between groups at a ratio of 1:1:1:1) will be compared: no home NIV 'hospital NIV' (control group) versus any of 3 modalities of home NIV (experimental groups). The 3 experimental treatments are Nocturnal home NIV 'non-targeted home NIV', Nocturnal home NIV with high monitoring 'targeted home NIV', and 'rescue home NIV'.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The hypothesis of this study is that any of 3 modalities of home non- invasive ventilation (NIV) compared to 'no NIV' (=hospital NIV) will reduce re-admission to hospital or death in COPD patients who remain persistently hypercapnic following an exacerbation requiring NIV.

Detailed description: By 2020, chronic obstructive pulmonary disease (COPD) is expected to be the 3rd leading cause of death in the world, especially in countries of middle to high income, like EU. Despite the improvements in survival by using acute non- invasive ventilation (NIV) to treat patients with exacerbations of COPD complicated by acute hypercapnic respiratory failure (AHRF), these patients are at high risk of re-admission and further life-threatening events. Furthermore, in a recent study of 110 patients who had AHRF (RESCUE study, Struik, Thorax 2014), at one year after discharge 65% had another life-threatening event, and 49% had died. New recent data suggests that NIV at home can reduce re-admissions (HMV-LTOT, Murphy, JAMA 2017), but in a small proportion of patients, and with a high level of expertise. There is an urgent need to develop strategies to reduce the number and severity of exacerbations of COPD. With healthcare objectives and budget constraints, telemonitoring of COPD patients is an important challenge in most European countries. RESCUE2-Monitor is the next step. This European trial (currently, France, Spain and Portugal) will test the hypothesis that home NIV, with a highly adapted ventilatory strategy (hereafter referred to as 'TARGETED VENTILATION'), compared to no home NIV (only hospital NIV), to non-targeted home NIV or to rescue home NIV will reduce re-admission to hospital or death in COPD patients, is possible using e-medicine, and will reduce costs of health.

Eligibility criteria: Inclusion Criteria:

* 1) Patients with COPD, GOLD C or D and Forced expiratory volume in one second (FEV1)\<65%;
* 2) AHRF (pH\<7,35 and PaCO2≥45mm Hg (≥6kPa) treated more than 24h with Ventilation (non-invasive or invasive);
* 3) 48h to 2 weeks with pH\>7.35, and PaCO2\>45 (\>6kPa) after NIV withdrawal, during daytime at rest without oxygen or ventilatory support (or with O2 if patients are not able to avoid O2 with immediate desaturation below 80%).

Exclusion Criteria:

1. Patient treated with chronic NIV or continuous positive airway pressure (CPAP) device, with ongoing treatment;
2. Primary diagnosis of restrictive lung disease causing hypercapnia i.e. obesity hypoventilation and chest wall disease, however these patients will be included if the "FEV1/Forced vital capacity (FVC)" ratio is \<60% and the FEV1 \<50% if the predominant defect is considered to be obstructive by the center clinician;
3. BMI \> 35 kg/m2;
4. Sedative medication causing hypercapnia (\> 3 drugs or more than 20mg of morphine/day);
5. Polygraphic diagnosis of Obstructive Sleep Apnoea Syndrome (AHI\>30/h (French criteria);
6. Cognitive impairment that would prevent informed consent into the trial
7. Pregnancy;
8. Tobacco use \< 10 pack-year;
9. Psychiatric disease necessitating anti-psychotic medication, ongoing treatment for drug or alcohol addiction, persons of no fixed abode post-discharge;
10. Unstable coronary artery syndrome;
11. Age \<18 years;
12. Inability to comply with the protocol;
13. Expected survival\<12 months due to any situation other than COPD disease;
14. Duration of ICU stay\>10 days;
15. No affiliated to national health insurance;
16. Measure of legal protection (guardianship, wardship or judicial protection) for patients over the age of majority.

Primary outcomes:
measure: admission-free survival
timeFrame: 0-36 months
Secondary outcomes:
measure: Overall survival
timeFrame: 0-36 months
measure: Frequency of exacerbations requiring hospitalization
timeFrame: 12 months
measure: Frequency of exacerbations resulting in physician directed treatment
timeFrame: 12 months
measure: Assessment of Exacerbation based on changes in arterial pressure of carbon dioxide
timeFrame: 0, 1, 3, 6, 12, 18, 24, 30 and 36 months
measure: Assessment of Exacerbation based on changes in arterial partial pressure of oxygen
timeFrame: 0, 1, 3, 6, 12, 18, 24, 30 and 36 months
measure: Assessment of Quality of life with St George's respiratory questionnaire
timeFrame: 0,1, 3, 6, 24 and 36 months
measure: Assessment of Quality of life with Severe Respiratory Insufficiency Questionnaire
timeFrame: 0,1, 3, 6, 24 and 36 months
measure: Assessment of Quality of life with SF-36
timeFrame: 0,1, 3, 6, 24 and 36 months
measure: Assessment of Quality of life with the 5-level EQ-5D version
timeFrame: 0,1, 3, 6, 24 and 36 months
measure: Assessment of Quality of life with the Charlson Comorbidity Index
timeFrame: 0,1, 3, 6, 24 and 36 months
measure: Assessment of Quality of life with the COPD Assessment Test (CAT)
timeFrame: 0,1, 3, 6, 24 and 36 months
measure: Assessment of Quality of sleep with Pittsburgh Sleep Quality Index
timeFrame: 0,1, 3, 6, 24 and 36 months
measure: Assessment of Quality of sleep with Epworth Sleepiness Scale
timeFrame: 0,1, 3, 6, 24 and 36 months
measure: Assessment of dyspnea with Modified Medical Research Council (mMRC) scale
timeFrame: 0,1, 3, 6, 24 and 36 months
measure: Adverse events (AEs) frequency
timeFrame: 0, 3, 6, 12, 18, 24 and 36 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpêtrière-Charles Foix
state: Ile-de-France
Study officials:
affiliation: Hôpital Pitié Salpêtrière-Charles Foix, Paris, France ,
name: Jesus Gonzalez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rescue2-monitor group. Respiratory support in COPD patients after acute exacerbation with monitoring the quality of support (Rescue2-monitor): an open-label, prospective randomized, controlled, superiority clinical trial comparing hospital- versus home-based acute non-invasive ventilation for patients with hypercapnic chronic obstructive pulmonary disease. Trials. 2020 Oct 22;21(1):877. doi: 10.1186/s13063-020-04672-w.