Study of the Efficacy of Home Mechanical Ventilation Post Acute Hypercapnic Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2012 by Guy's and St Thomas' NHS Foundation Trust
Sponsor:
Collaborators:
Guy's & St Thomas' Charity
Respironics International
ResMed
ResMed Foundation
Information provided by (Responsible Party):
Patrick Murphy, Guy's and St Thomas' NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00990132
First received: October 5, 2009
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

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).


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Device: Non invasive ventilation
Device: LTOT
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomised Controlled Trial of Home Mechanical Ventilation in Hypercapnic Chronic Obstructive Pulmonary Disease Patients Post Acute Hypercapnic Exacerbation

Resource links provided by NLM:


Further study details as provided by Guy's and St Thomas' NHS Foundation Trust:

Primary Outcome Measures:
  • Days from trial intervention to either hospital admission or death [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Spirometry - specifically FEV1 & FVC change from trial intervention to follow up. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Change in arterial PaCO2 from pre-intervention to follow up [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Change in the incremental shuttle walk test from pre-intervention to follow up [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Frequency of acute exacerbations of COPD requiring addition of antibiotics and or steroids and or hospital admission [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 116
Study Start Date: October 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Long term oxygen therapy
LTOT will be established as per current national guidelines
Device: LTOT
LTOT established as per national guidelines
Experimental: Home mechanical ventilation
Patients will be set up on LTOT as per national guidelines and nocturnal non-invasive ventilation in accordance with study protocol.
Device: Non invasive ventilation
Nocturnal non-invasive ventilation
Other Names:
  • Harmony 2
  • VPAP III STA

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990132

Contacts
Contact: Nicholas Hart, PhD nicholas.hart@gstt.nhs.uk
Contact: Patrick Murphy, MBBS 02071888070 patrick.murphy@gstt.nhs.uk

Locations
United Kingdom
Papworth Hospital Not yet recruiting
Cambridge, United Kingdom
Contact: Ian Smith       ian.smith@papworth.nhs.uk   
St James' University Hospital Not yet recruiting
Leeds, United Kingdom
Contact: Mark Elliot       mwelliot@doctors.org   
King's College Hospital Not yet recruiting
London, United Kingdom
Contact: John Moxham, MD       john.moxham@kcl.ac.uk   
Contact: Patrick Murphy, MBBS    02071888070    patrick.murphy@gstt.nhs.uk   
Sub-Investigator: Patrick Murphy, MBBS         
Royal Free Hospital / University College London Not yet recruiting
London, United Kingdom
Contact: Wisia Wedzicha       wwedzich@medsch.ucl.ac.uk   
Guy's & St Thomas' NHS Foundation Trust Recruiting
London, United Kingdom, SE1 7EH
Contact: Nicholas Hart, PhD       nicholas.hart@gstt.nhs.uk   
Contact: Patrick Murphy, MBBS    02071888070    patrick.murphy@gstt.nhs.uk   
Principal Investigator: Patrick Murphy, MBBS         
Royal Brompton & Harefield NHS Foundation Trust Not yet recruiting
London, United Kingdom
Contact: Michael Polkey, PhD       m.polkey@rbht.nhs.uk   
Contact: Patrick Murphy, MBBS    02071888070    patrick.murphy@gstt.nhs.uk   
Sub-Investigator: Patrick Murphy, MBBS         
John Radcliffe Hopsital Not yet recruiting
Oxford, United Kingdom
Contact: John Stradling       john.stradling@orh.ox.ac.uk   
Sponsors and Collaborators
Patrick Murphy
Guy's & St Thomas' Charity
Respironics International
ResMed
ResMed Foundation
Investigators
Principal Investigator: Patrick Murphy, MBBS Guy's & St Thoams' NHS Foundation Trust
Study Chair: Nicholas Hart, PhD Guy's and St Thomas' NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Patrick Murphy, Clinical Research Fellow, Guy's and St Thomas' NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00990132     History of Changes
Other Study ID Numbers: RJ1 09/N070
Study First Received: October 5, 2009
Last Updated: May 17, 2012
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: National Health Service

Keywords provided by Guy's and St Thomas' NHS Foundation Trust:
COPD
Respiratory failure
Non-invasive ventilation
Home mechanical ventilation

Additional relevant MeSH terms:
Hypercapnia
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Signs and Symptoms, Respiratory
Signs and Symptoms
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 25, 2014