Comparing standard and accelerated weaning from non-invasive breathing support in exacerbation of chronic obstructive pulmonary disease

INTERVENTION: Patients with exacerbation of COPD requiring NIV who have low or medium risk NIV outcomes scores will be assessed against the full selection criteria detailed below. Consenting patients who meet the eligibility criteria will be independently randomised on a 1:1 basis between the two treatment strategies, performed independently (sealedenvelope.com) using minimisation to ensure groups are balanced for: a) NIV Outcomes score: low or medium risk; b) Site; c) HCO3‐: <28 or =28; d) pH: <7.18 or =7.18; e) previous NIV: yes or no. Standard weaning protocol: Progressively longer periods off NIV, determined by arterial blood gas (or capillary blood gas), with a final night on NIV after a full day off NIV. Accelerated weaning protocol: Daily 4‐hour weaning trial, success confirmed by arterial blood gas, with additional transcutaneous carbon dioxide monitoring. The weaning time endpoint is the date and time that the NIV mask is removed from the patient’s face for the final time (provided NIV does not need to be recommenced within 48 hours). CONDITION: Exacerbation of chronic obstructive pulmonary disease (COPD) ; Respiratory ; Other chronic obstructive pulmonary disease PRIMARY OUTCOME: Time to successful weaning: duration from the baseline arterial blood gas confirming selection criteria met, to final removal of the ventilator. Death on NIV precludes weaning and will be captured in a competing risk analysis. INCLUSION CRITERIA: 1. Clinical diagnosis of Exacerbation of Chronic Obstructive Pulmonary Disease, complicated by acute hypercapnic respiratory failure (pH <7.35 and PaCO2 >6.5 kPa) 2. Age 35 years or over 3. Smoking history of 10 or more pack years 4. Low or medium risk Non‐Invasive Ventilation (NIV) Outcomes score 5. Provision of acute NIV for 24 hours or longer 6. Correction of respiratory acidaemia 7. PaCO2 <8 kPa, or PaCO2 8‐9 kPa with at least a 20% fall in PaCO2 from pre‐NIV baseline value 8. Able to tolerate 60 minutes of unsupported breathing, confirmed by arterial blood gas (ABG) 9. Participants must be randomised within 24 hours of meeting the weaning criteria (based on the time of the qualifying ABG) SECONDARY OUTCOME: ; 1. Relapse requiring NIV (defined as recurrent acute hypercapnic respiratory failure (AHRF) >48 hours after removal of the ventilator); 2. Total duration of ventilation measured from the time the NIV mask is applied to NIV mask removal; 3. Length of hospital stay from arrival to discharge measured using medical records/hospital patient administration system; 4. NIV complications (incidence and severity) in hospital, measured by daily recording; 5. Patient‐reported outcome measures at days 7, 30 and 90 post‐randomisation:; 5.1. How breathless the patient feels, measured using the Modified Borg dyspnoea scale; 5.2. Sputum clearance measured using a visual analogue scale; 5.3. How well or poorly the patient feels they have slept the previous night, measured using the Richards‐Campbell sleep questionnaire (all measured days 1 to 5 from the start of weaning); 5.4. Patient’s mood for anxiety and depression measured using the Hospital Anxiety and Depression Scale (HADS) pre‐discharge; 5.5. Quality of life related to COPD measured using the St Georges Respiratory Questionnaire for COPD (SGRQ‐C); 5.6. Quality of life measured using EQ‐5D‐5L; 6. Mortality in‐hospital and 90‐days post‐randomisation measured using medical and GP records/electronic patient administration system; 7. Readmissions 30‐days post‐discharge measured using patient self‐completed health resource use diary and verified with hospital electronic patient administration system and primary care records; 8. Health economic analysis:; 8.1. Costs to the NHS in terms of provision of the interventions (both on a respiratory support unit and a critical care unit) and cost implications of subsequent resource utilisation up to 90 days follow‐up measured by patient health resource use diaries; 8.2. Cost‐utility analysis using EQ‐5D‐5L quality‐adjusted life years (QALYs) measured by questionnaire at 30 and 90 days post‐randomisation; 9. Responder analysis within the accelerated weaning group to identify predictors of success/failure;