REgistry-based Randomized Controlled Trial of Treatment Duration and Mortality in Long-term OXygen Therapy (REDOX) A Multicenter, Phase IV, Registry-Based, Randomized Controlled Trial (R-RCT)
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Skane University Hospital
- Enrollment
- 241
- Locations
- 2
- Primary Endpoint
- All-cause hospitalization or mortality rate
Study Overview
Brief Summary
Multicenter, phase IV, non-superiority, registry-based, randomized controlled trial. Patients starting long-term oxygen therapy (LTOT) are randomized between LTOT prescribed 24 h/day or 15 h/day using the Swedish Register for Respiratory Failure (Swedevox). Clinical follow-up and concurrent treatments are according to routine clinical practice. The main endpoints of mortality, hospitalizations, and incident disease are assessed using Swedish registry data, with expected complete follow-up. Patient-reported outcomes are assessed using a posted questionnaire at 3 and 12 months. The study is managed by the Uppsala Clinical Research Centre (UCR).
Detailed Description
BACKGROUND:
LTOT given 15 h/day or more improves the survival time in patients with chronic daytime hypoxemia due to chronic obstructive pulmonary disease (COPD) based on two randomized trials; the 'Continuous or Nocturnal Oxygen Therapy' Trial (NOTT) published in 1980 [1] and the Medical Research Council (MRC) trial published in 1981.[2] International guidelines recommend that LTOT is prescribed continuously (24 h/day), which is based on an observational, unadjusted comparison of the treatment arms of the MRC and NOTT studies only. [3] However, LTOT 24 h/day may place an unnecessary burden on patients in terms of increased dependence, isolation, side effects and restricted activity.[3, 4] Data from the National Swedish Registry for Respiratory Failure (Swedevox) indicate no survival benefit from LTOT 24 vs 15 h/day (Figure 1). No randomized trial has evaluated the additional benefit of longer daily duration of LTOT above 15 h/day.[4] Studies on the effect of LTOT are also lacking for diseases other than COPD, such as pulmonary fibrosis, yet LTOT is given in these conditions according to the same criteria as in COPD in clinical practice.[4]
IMPORTANCE:
This will be the first R-RCT in respiratory medicine and the largest trial of LTOT to date. If LTOT 24 h/day is found to be superior to 15 h/day, this will confirm the importance of oxygen therapy in chronic respiratory failure and the importance of implementing services to optimize the daily duration of LTOT. If LTOT 24 h/day is non-superior to 15 h/day, this supports that patients safely can be free of supplemental oxygen for up to nine hours per day. This trial will also be the first to evaluate effects of LTOT on symptoms and HRQOL, effects in patients with moderate hypoxemia and in diseases other than COPD. This study will have direct impact on research and clinical management.
AIM:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18 years or older
- •Severe resting hypoxemia (PaO2 < 7.4 kPa or oxygen saturation < 88% breathing air), or PaO2 < 8.0 kPa on air and either signs of heart failure or polycythemia (EVF > 0.54).
Exclusion Criteria
- •Smoking or contact with open fire
- •Other inability to safely comply with LTOT
- •Already on LTOT for more than 28 days
- •Inability to comply with any of the study interventions as judged by the responsible oxygen staff
- •Opt out from being registered in Swedevox
- •Inability to give informed written consent to participate in the study as judged by the oxygen responsible staff
- •Lack of Swedish identification number
- •Previous participation in the study.
- •Patient populations that will be evaluated:
- •Primary analysis: In all randomized patients according to the intention-to-treat and per protocol principles.
- •Secondary analyses: In patients with 1) PaO2 (air) < 7.4 kPa; 2) PaO2 (air) 7.4 to 8.0 kPa; 3) COPD verified by spirometry (COPD as primary diagnosis and FEV1/FVC < 0.7 after bronchodilation); 4) and in patients with a primary diagnosis other than COPD.
Arms & Interventions
LTOT 24 h/day (intervention)
Long-term oxygen therapy (LTOT) prescribed 24 h/day. The LTOT is provided according to standard clinical practice using oxygen concentrator, cylinders or liquid oxygen and administered mainly through nasal prongs. The oxygen dose (l/min) is titrated aiming at a PaO2 on oxygen > 8 kPa in accordance with current routine practice and management guidelines.
Intervention: LTOT 24 h/day (Drug)
LTOT 15 h/day (control)
Long-term oxygen therapy (LTOT) prescribed 15 h/day. The LTOT is provided according to standard clinical practice using oxygen concentrator, cylinders or liquid oxygen and administered mainly through nasal prongs. The oxygen dose (l/min) is titrated aiming at a PaO2 on oxygen > 8 kPa in accordance with current routine practice and management guidelines.
Intervention: LTOT 15h/day (Drug)
Outcomes
Primary Outcomes
All-cause hospitalization or mortality rate
Time Frame: 1 year
To determine whether oxygen prescribed 24 h/day compared with 15 h/day in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia improves the rate of all-cause hospitalization or mortality at 1 year.
Secondary Outcomes
- All-cause mortality rate(3 months and 12 months)
- Mortality rate from respiratory disease(3 months and 12 months)
- Mortality rate from cardiovascular disease(3 months and 12 months)
- Hospitalization rate from all causes(3 months and 12 months)
- Hospitalization rate with a primary diagnosis of cardiovascular disease(3 months and 12 months)
- Hospitalization rate with a primary diagnosis of respiratory disease(3 months and 12 months)
- Rate of an incident diagnosis of cardiovascular disease(3 months and 12 months)
- Self-reported questionnaire data on oxygen use(3 months and 12 months)
- Self-reported questionnaire data on physical activity(3 months and 12 months)
- Self-reported questionnaire data on LTOT continuation(3 months and 12 months)
- Self-reported questionnaire data on breathlessness (MDP scale)(3 months and 12 months)
- Self-reported questionnaire data on breathlessness (mMRC scale)(3 months and 12 months)
- Self-reported questionnaire data on fatigue (FACIT-Fatigue)(3 months and 12 months)
- Self-reported questionnaire data on cognition (BAS)(3 months and 12 months)
- Self-reported questionnaire data on HRQOL (CAT)(3 months and 12 months)
- Self-reported questionnaire data on HRQOL (EQ-5D-5L)(3 months and 12 months)
- Self-reported questionnaire data on treatment response (GIC)(3 months and 12 months)
- Health care utilization(3 months and 12 months)
Investigators
Magnus Ekström
Principal Investigator
Skane University Hospital