Clinical trial NCT00990132: Home Mechanical Ventilation vs Home Oxygen Therapy in COPD
Official title: Randomised Controlled Trial of Home Mechanical Ventilation in Hypercapnic Chronic Obstructive Pulmonary Disease Patients Post Acute Hypercapnic Exacerbation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Respiratory failure
Non-invasive ventilation
Home mechanical ventilation
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Guy's & St Thomas' Charity
name: Respironics International
name: ResMed
name: ResMed Foundation
First posted: 2009-10-06
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to investigate the effect of home mechanical ventilation (HMV) in patients with severe chronic obstructive pulmonary disease (COPD). The purpose of the trial is to test the hypothesis that HMV and longterm oxygen therapy (LTOT) increases admission free survival compared with LTOT alone. More specifically, compared with LTOT, HMV and LTOT reduces hospital re-admission in COPD patients who remain persistently hypercapnic following an acute exacerbation requiring non-invasive ventilation (NIV).

Detailed description: Although HMV has been shown to improve physiological parameters as well as have clinical benefits in terms of dyspnoea and exercise capacity in severe COPD, the published randomised controlled trials have been less positive. The Steering Committee are committed to design a robust clinical trial that will answer this clinical question. Therefore, a multi-centre randomised controlled trial has been designed with recruitment and power calculations based on the applicants own data.

We will recruit from 8 UK university centres with expertise in HMV, 116 hypercapnic patients (58 in each arm) with persistent hypercapnia following an episode of acute hypercapnic respiratory failure. During the acute hypercapnic episode the patient would have be eligible for non-invasive ventilation with a pH \<7.35 and a partial pressure of carbon dioxide (PaCO2) \> 7.0kPa. They will be randomised, for a 12 months, to either

1. HMV and LTOT (Treatment Group)
2. LTOT alone (Control Group) This study would allow the investigators to answer a number of questions pertaining to clinical efficacy of HMV in COPD as well as the mechanism of action of HMV in COPD

   * Does HMV effect admission-free survival?
   * Does HMV reduce exacerbation frequency?
   * Does HMV impact on disease progression?
   * Does HMV improve health-related quality of life?
   * Does HMV improve exercise capacity?
   * Is there a dose-response between hours of ventilator compliance and daytime PaO2 and PaCO2?
   * Do patients increase hours of ventilator use during acute exacerbations?
   * Is ventilator compliance with HMV and LTOT acceptable?
   * Does HMV reduce healthcare utilisation? Follow-up assessments will be performed at 6 weeks, 3, 6 and 12 months. These data collected will include admission-free survival (primary outcome), hours of compliance with HMV, HRQL, gas exchange, lung function, body composition, exercise capacity, exacerbation frequency primary care consultations and compliance with LTOT, time to withdrawal of LTOT/night-time oxygen therapy based on daytime PaO2 and overnight SaO2 (secondary outcome measures). The relation of any changes to factors predicting severity of COPD will be studied. The cost effectiveness and cost-utility analysis of HMV will be studied.

Eligibility criteria: Inclusion Criteria:

* Patients with COPD
* Acute hypercapnic exacerbation of COPD at least 2 weeks previously
* Tolerated non-invasive ventilation during acute hypercapnic exacerbation
* Chronic hypoxia requiring LTOT (PaO2 \<7.3kPa or a PaO2 \>7.3 and \<8.0kPa and one of the following: secondary polycythaemia; nocturnal hypoxaemia SaO2 \<90% for \>30% of the time; peripheral oedema; or PHT)
* Chronic hypercapnia (PaCO2 \>7kPa)
* ≥20 pack year smoking history
* FEV1/FVC \<60%
* FEV1 at \<50% predicted

Exclusion Criteria:

* Persistent hypercapnic respiratory failure with acidosis (defined as pH \<7.30 after bronchodilators)
* Development of worsening hypercapnic respiratory failure with acidosis during initiation of LTOT therapy
* Failure to tolerate NIV during the acute illness preceding trial identification
* Post extubation or decannulation following AHRF requiring intubation
* Restrictive lung disease causing hypercapnia i.e. obesity hypoventilation and chest wall disease, however these patients will be included if the FEV1/FVC ratio is \<60% and the FEV1 \<50% if the predominant defect is considered to be obstructive by the center clinician.
* Clinical features of severe OSA
* BMI \>35kg/m2
* Unstable coronary artery syndrome
* Cognitive impairment that would prevent informed consent into the trial
* Psychiatric disease necessitating anti-psychotic medication, ongoing treatment for drug or alcohol addiction, persons of no fixed abode post-discharge
* Patients undergoing renal replacement therapy
* Age \<18 years
* Pregnant
* Inability to comply with the protocol

Primary outcomes:
measure: Days from trial intervention to either hospital admission or death
timeFrame: 1 year
Secondary outcomes:
measure: Spirometry - specifically FEV1 & FVC change from trial intervention to follow up.
timeFrame: 1 year
measure: Changes Health related quality of life from pre-intervention to follow up - specifically outcomes of severe respiratory insufficiency questionnaire, chronic respiratory disease questionnaire & MRC dyspnoea score
timeFrame: 1 year
measure: Change in arterial PaCO2 from pre-intervention to follow up
timeFrame: 1 year
measure: Change in the incremental shuttle walk test from pre-intervention to follow up
timeFrame: 1 year
measure: Frequency of acute exacerbations of COPD requiring addition of antibiotics and or steroids and or hospital admission
timeFrame: 1 year
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Leeds
country: United Kingdom
facility: St James' University Hospital
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free Hospital / University College London
city: Oxford
country: United Kingdom
facility: John Radcliffe Hopsital
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Patrick Murphy, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Nicholas Hart, PhD
role: STUDY_CHAIR
References:
citation: Murphy PB, Rehal S, Arbane G, Bourke S, Calverley PMA, Crook AM, Dowson L, Duffy N, Gibson GJ, Hughes PD, Hurst JR, Lewis KE, Mukherjee R, Nickol A, Oscroft N, Patout M, Pepperell J, Smith I, Stradling JR, Wedzicha JA, Polkey MI, Elliott MW, Hart N. Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial. JAMA. 2017 Jun 6;317(21):2177-2186. doi: 10.1001/jama.2017.4451.