Home Non Invasive Ventilation (NIV) Treatment for COPD-patients After a NIV-treated Exacerbation
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- Enrollment
- 150
- Locations
- 8
- Primary Endpoint
- Time to death or repeat AHRF with need of NIV
Study Overview
Brief Summary
Background: In chronic obstructive pulmonary disease, the prognosis for patients who have survived an episode of acute hypercapnic respiratory failure due to an exacerbation is poor. Despite being shown to improve survival and quality-of-life in stable patients with chronic hypercapnic respiratory failure, long-term noninvasive ventilation is controversial in unstable patients with frequent exacerbations, complicated by acute hypercapnic respiratory failure. In an uncontrolled group of patients with previous episodes of acute hypercapnic respiratory failure, treated with noninvasive ventilation, we have been able to reduce mortality and the number of repeat respiratory failure and readmissions by continuing the acute noninvasive ventilatory therapy as a long-term therapy.
Methods: Multi-center open label randomized controlled trial of 150 patients having survived an admission with noninvasive ventilatory treatment of acute hypercapnic respiratory failure due chronic obstructive pulmonary disease. The included patients are randomized to usual care or to continuing the acute noninvasive ventilation as a long-term therapy, both with a one-year follow-up period.
End points: The primary endpoint is one-year mortality; secondary endpoints are time to death or repeat acute hypercapnic respiratory failure, number of readmissions and repeat acute hypercapnic respiratory failure, exacerbations, dyspnea, quality of life, sleep quality, lung function, and arterial gases.
Detailed Description
Background Noninvasive ventilation (NIV) has been shown to improve survival in patients with chronic obstructive pulmonary disease (COPD), admitted with acute hypercapnic respiratory failure (AHRF); and NIV is recommended as a treatment of AHRF due to COPD. COPD patients having survived AHRF have a poor prognosis; Chu et al. have shown one-year risks of readmission of 79.9%; of a new life-threatening event (death or repeat AHRF) of 63.3%; and of death of 49.1%.
Hypothetically, long-term NIV (LTNIV) can improve the prognosis for severe COPD. The majority of trials have focused on patients with chronic hypercapnic respiratory failure due to stable COPD (i.e., patients with no exacerbations prior to LTNIV initiation); and their results have been conflicting. However, in 2014, Köhnlein et al. published the results of a large randomized controlled trial (RCT) of LTNIV for stable patients with an arterial CO2 tension (Pa,CO2) of 7 kPa or higher: The patients treated with LTNIV had a one-year mortality of 12% vs. 33% for the controls; and the patients treated with LTNIV scored higher in health-related quality-of-life (HRQoL).
Three RCTs have studied the effects of LTNIV for unstable COPD, i.e., where the participants were enrolled after an admission with NIV treatment of AHRF: Cheung et al. and found that the patients treated with LTNIV had a lower rate of repeat AHRF (38.5%/year vs. 60.2%/year, p = 0.039); and Funk et al. found that the LTNIV group had a longer mean time to clinical worsening (391 days vs. 162 days; p = 0.0018). However, the largest RCT by Struik et al., showed no differences between the LTNIV group and the controls.
Little is known of what predicts AHRF in severe COPD. However, based on the large ECLIPSE study on exacerbations of COPD, Hurst et al. and Müllerova et al. showed that previous exacerbations predict new exacerbations; and that previous admissions due to exacerbations of COPD predict new admissions and death.
We assume that previous admissions with AHRF due to COPD could predict new admissions with AHRF and need of NIV, as well as death.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patient admitted with a NIV-requiring exacerbation of COPD
- •COPD with a FEV1/FVC <0.7 after bronchodilatation.
- •≥ 1 acute hypercapnic respiratory failure (AHRF *).
- •Optimal medical treatment of COPD, ie. inhaled steroids, long-acting β2-agonist Tiotropium, according to GOLD guidelines.
- •Address in Capital Region
- •Patients are able to give verbal consent and sign a written consent form and understand Danish-
Exclusion Criteria
- •Severely depressed level of consciousness / confusion / non-cooperative.
- •Respiratory rate <12/min
- •Severe hypoxia, such as requiring more than 15L O2/min.
- •Large amounts of sputum.
- •Vomiting and high risk for aspiration.
- •Inability to accept NIV.
- •Recent abdominal, facial or upper airway surgery.
- •Malignancy or life expectancy <6 months because of disease other than COPD
- •Known obstructive sleep apnea syndrome (OSA)
- •Metabolic acidotic component - StHCO3- < 20 mM
Arms & Interventions
LTNIV group
LTNIV group is discharged with the ventilator and the settings and pressures which reversed the respiratory failure and the hypercapnic acidosis. We know the patients are able to tolerate these settings. The ventilators are Philips A30. The patients must use the ventilator for a minimum of six hours a night.
Furthermore, the patients are discharged with usual care, i.e., the golden standard of COPD treatment as described in GOLD-guidelines.
Outpatient visits are given every three months.
Intervention: LTNIV (Device)
Control group
Patients in the control group are discharged with usual care, i.e., the golden standard of COPD treatment as described in GOLD-guidelines.
Outpatient visits are given every three months.
Outcomes
Primary Outcomes
Time to death or repeat AHRF with need of NIV
Time Frame: 1 year
Measured by Kaplan Meier plot and log rank with a Cox proportional hazards regression. Intention-to-treat analysis. Secondarily, mortality will be analyzed as Per-protocol as well
Secondary Outcomes
- Hospitalizations (time to - and absolute number)(1 year)
- Health related quality of life(1 year)
- medication status(1 year)
- Dyspnea(1 year)
- Number of contacts with ER, GP because of COPD(1 year)
- Number of days admitted(1 year)
- Mortality(1 year)
- Number of repeat AHRF with need for NIV(1 year)
Investigators
Kasper Linde Ankjaergaard, MD
MD. ph.d-student
University Hospital, Gentofte, Copenhagen