Home Non Invasive Ventilation (NIV) Treatment for COPD-patients After a NIV-treated Exacerbation

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by University Hospital, Gentofte, Copenhagen
Sponsor:
Collaborator:
Philips Respironics
Information provided by (Responsible Party):
Kasper Linde Ankjaergaard, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01513655
First received: January 16, 2012
Last updated: December 4, 2014
Last verified: December 2014
  Purpose

Chronic Obstructive Pulmonary Disease, COPD, is characterized by chronic impaired function and capacity of the lungs and airways. COPD and graded from mild to very severe COPD. Colds, inhalation of dust and pollen as well stay in the cold can cause a worsening, a so-called exacerbation in which the airways become inflamed, constricted and filled with secretions. The patient's ability to maintain adequate respiration is affected dramatically and hospitalization is required. The condition treated medically, but in severe cases, it is so critical to patient needs acute respiratory support or NIV (non invasive ventilation).

NIV is a very gentle mask respirator principle, whereby the patient's own breathing supported and does not require anesthesia. A mesh connects the mouth and nose so that the changing air pressure helps the air through the narrowed airways.

Background Normally NIV therapy is used only during hospitalization. Evidence suggests, however, that home NIV treatment of patients who have previously been admitted with a NIV-requiring exacerbation of COPD, may prevent the majority of exacerbations and admissions for this. Furthermore seem home NIV to reduce mortality among COPD patients. This technique increases both safety and quality of life for a group of very vulnerable patients. The effect is not documented. In this project the investigators want to investigate this effect.

The project in practice In practice, the investigators ask all patients admitted with an exacerbation NIV-consuming in the Capital Region, if they want to participate. If the patient wants this, pull the left as to whether he / she will receive usual care (which is internationally approved gold standard) or usual care + NIV. It is here supposed, the patient must sleep with NIV mask on every night.

Both groups attached to the same follow-up in outpatient clinic and a telephone hotline and receive exactly the same care and attention - except for the NIV. Thereby all the differences in the two groups such as the quality of life, functioning, hospitalization frequency, medication use, and especially mortality are certain to be due to the NIV treatment.

The above mentioned are the end points of this study


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Acute Exacerbation of Chronic Obstructive Airways Disease
Chronic Hypercapnic Respiratory Failure
Device: Nightly NIV for at least 6 hours
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Home Non Invasive Ventilation (NIV) Treatment for COPD-patients After a NIV-treated Exacerbation

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • Mortality [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Measured by Kaplan Meier plot and logrank as an Intention-to-treat analysis. Secondarily, mortality will be analyzed as Per-protocol as well


Secondary Outcome Measures:
  • Hospitalization frequency [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Measured by Kaplan Meier plot, logrank and absolute data. Both ITT and PP

  • Health related quality of life [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    measured by the CAT and SRI questionnaires

  • medication status [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    use of medication during one year's follow-up

  • Dyspnea [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The MRC dyspnea scale

  • Number of contacts with ER, GP because of COPD [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Number of days admitted [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: July 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NIV group

NIV group is given golden standard COPD care as described in GOLD-guidelines + nocturnal noninvasive ventilation at home as the study intervention.

Ventilator settings match the settings on which the patient obtained a normalization of pH and normocapnia during the last episode of acute hypercapnic respiratory failure.

Outpatient visits are given every three months

Device: Nightly NIV for at least 6 hours
NIV given on Philips BiPAP Synchrony apparatus. Adjusted by local dept. of pulmonary medicine.
Other Names:
  • BiPAP A30 AVAPS - Philips Respironics
  • SmartCard reader 1003543
No Intervention: Control Group

Control Group is given golden standard COPD care as described in GOLD-guidelines.

Outpatient visits are given every three months


  Hide Detailed Description

Detailed Description:

Noninvasive positive-pressure ventilation (NIV) has been shown to improve survival significantly (1) in patients with chronic obstructive pulmonary disease (COPD), hospitalized for acute exacerbation and complicated with acute hypercapnic respiratory failure (AHRF). Similarly, NIV reduces complications such as pneumonia, compared with invasive ventilation. NIV is recommended as first-line treatment in these patients (GOLD guidelines). The risk of readmission after an AHRF treated with NIV is 80% within the first year, the risk of a life threatening event is 63% and the risk of death is 49% (2).

In univariate analyzes, survival of chronic hypercapnic COPD patients treated with NIV at home correlates with age, BMI, Hb, FEV1, specific airway resistance, hyperinflation, pH, BE; and in multivariate analysis significantly with age, BMI , hyperinflation and BE(3).

No previous studies of home NIV in COPD patients - except one (4) - have used previous acute NIV treatment as an inclusion criterion, and the results have been conflicting. The largest RCT of home NIV found a small but significant reduction in mortality - apparently at the expense of quality of life (5). This study included stable hypercapnic COPD patients treated with Long Term Oxygen Treatment without previous NIV treatment. One possible explanation for the reduced quality of life may be that the patients had not previously experienced a severe acute NIV-dependent exacerbation in COPD with associated anxiety and loss of quality of life. This maybe caused the high patient dropout in the home NIV group.

In the only RCT in which the inclusion criterion was a previous acute NIV-treated exacerbation of COPD, home NIV reduced the number of admissions and exacerbations (4). The study was small (23+24 patients), and quality of life was not investigated. Hypercapnia was not an inclusion criterion.

Home NIV treatment of COPD aims at a normalization of PaCO2 and BE, and both randomized and observational studies have shown that this can happen with high levels of Inspiratory Positive Airway Pressure (IPAP) up to 28 cm of water and Expiratory Positive Airway Pressure (EPAP) 5 cm of water(6).

We evaluated our patients who received NIV at home, after at least two NIV-treated AHRFs and found a significant in re-AHRFs, readmissions and admission days, comparing the year following home NIV initiation with the year prior to initiation.

The aim of this RCT is to investigate whether home NIV - as an exacerbation prophylaxis - may reduce mortality in COPD patients after first acute NIV treatment and secondarily reduce both exacerbations and hospitalizations and improve the quality of life.

We find that sham NIV or CPAP in the control group could have a negative effect on quality of life and thus favor the NIV treatment group. Likewise, we believe that by offering the same outpatient monitoring in the two arms, and as our primary outcome is mortality, the risk of bias in an open trial will be minimal.

In order to reduce dropout rates in the NIV group, we evaluate the effect of the treatment after one month. Here, some patients will be permitted to pause the treatment. Below are listed the criteria for permissible pausation, as well as resume of the NIV therapy.

Eligibility criteria: See relevant section By readmissions, patients who have previously entered into the study will not be re-randomized. They continue in the study, and, if the patient is in the intervention group, home NIV is resumed if stopped.

Design The study is a randomized, controlled, open-label study with an intervention group (NIV) and a control group without NIV (usual care). Patients are included during admission. Patients receive home visits by a nurse after 1 week and the possibility of acute telephone by a nurse in week days.

Outpatient visits are 1, 3, 6, 9 and 12 months after discharge. A total of 150 patients will be included from the regional departments of pulmonary medicine. Patients are randomized 1:1 to either home NIV or usual care. Each center should have at least 15 patients.

Randomization is carried out using a computer-generated block randomization list for each center. The randomization list is stored at Gentofte Hospital in a sealed envelope. 50 sealed envelopes are prepared for each. center, each containing an individual code.

Sample size calculation Mortality during the first year among COPD patients with NIV treatment of AHRF is 49% (2), but mortality is greatest during the first 3 months (ca. 30%) (2) Since COPD patients with a life expectancy of less than 6 months due to other diseases than COPD are excluded from this study, we expect the 1-year mortality in the control group to be 40%. Minimum relevant difference (MIREDIF) after 12 months is set at 40% reduction in mortality (ie mortality in the control group = 0.40 and the NIV group = 0.24). Type 1 error (α) is set to 0.05 and type 2 error (β) is set to 0.9. The required sample size is computed to 37, but in order to ensure that the strength to detect the difference in the quality of life, 75 patients are included in each arm.

Outcome: See relevant section

Intervention

Standard care in both intervention and control group:

During hospitalization:

  • Acute NIV treatment of AHRF
  • Informed consent and randomization when the patient is stabilized and able to complete the acute NIV treatment
  • Standard medical treatment of exacerbation according to GOLD
  • Start of standard medical treatment, including smoking cessation program according to GOLD.
  • Patients are offered COPD rehabilitation in outpatient visits
  • Home visits by nurse 1 week after discharge.
  • Outpatient visits after 1, 3, 6, 9 and 12 months.
  • Associated nurse and emergency telephone hotline weekdays. 8 - 15 Only the intervention group
  • Home NIV initiated as a direct continuation of the acute NIV treatment during hospitalization
  • Home NIV optimized and IPAP is increased to the maximum value, the patient can accept.
  • Patients and caregivers are trained in handling and cleaning of the NIV apparatus, tubes, masks, etc.
  • Patients are encouraged to a minimum of 6 hours of daily use of NIV.
  • At the home visits and outpatient visits, NIV is optimized for patient requests / complaints.
  • At the first outpatient visit at one month, patients are evaluated by the nurse. Patients who have had only one AHRF treated with NIV and who do not feel a subjective improvement after one month of NIV are offered to pause the NIV therapy - provided they have not had any of the following in the first month:

Exacerbation; need for antibiotics or increased steroid; hospitalization; emergency room visits, or emergency doctor visits due to COPD; fever > 38˚C > 1 day; more or more purulent sputum > 1 day; Increased dyspnea > 1 day.

If it is agreed to pause the NIV therapy, the patient has to resume NIV at one or more of the above symptoms Measurements at startup

  • Arterial blood gasses (ABG)
  • Blood Tests
  • ECG
  • Chest x-ray

Measurements at discharge:

  • Lung function
  • SpO2%
  • ABG
  • Oxygen supply
  • Height and weight
  • MRC dyspnea score
  • CAT, and SRI
  • ESS
  • NIV-device SIM card read with regards to compliance (hours used per day) and apnea-hypopnea index
  • Medication Status

Measurements at outpatient visits 1, 3, 6, 9 and 12 months after discharge:

  • Lung function
  • SpO2%
  • ABG
  • Oxygen supply
  • Weight
  • MRC dyspnea score
  • CAT and SRI
  • NIV-device SIM card read with regards to compliance (hours used per day) and apnea-hypopnea index
  • Medication Status
  • ESS
  • Tobacco Status
  • Medication Status
  • Data is collected on mortality, hospital admissions, emergency room visits each outpatient visit and at the end of the .
  • IPAP, EPAP and BPM are optimized in order to normalize the ABG

Measurements at the home visit 1 week after discharge:

  • Lung function
  • SpO2%
  • Control of the NIV apparatus
  • Ensure that the patient is informed and uses the machine properly

Data Processing:

The primary outcome is the decrease in 1-year mortality in the home NIV group compared with the control group. Analyzed as an Intention-To-Treat analysis and calculated by the Kaplan-Meier plot and logrank.

Differences between active NIV treatment (intervention) and usual care (control) are measured during the intervention period (1 year). These differences in trends over time between intervention and control group are analyzed by analysis of variance (ANOVA) for repeated measures with a significance level of p <0.05. Statistically significant differences as analyzed using the t test for normal data

Publications:

Study results will be published in national and international journals and at conferences. This applies to both positive and negative results.

If negative results can not be published in journals, they will be published in other ways, such as on congresses.

Ethics:

The study was approved by the Research Ethics Committee, Data Protection, Clinical Trial and Drug Authority

Consent:

Informed consent is obtained after written and verbal information given by one of the attending physicians at the department. Once the acute situation is stable and the patient is ready, he is asked if he is interested in participating. Typically 2 days after admission, although this is individual. The patient is informed about the possibility of bringing a companion to the information interview.

The information interview is conducted in a single room with a physician who has devoted time to do so and thus not disturbed. There will be time allocated for informed consent and to ask questions and then signed consent form by both parties. If the participant wishes time for consideration, a new interview will be planned 1-2 days later. Consent sought for the discharge.

Biological material:

ABGs are analyzed after sampling and are destroyed immediately hereafter as a default for hospitalization and outpatient visits. Samples are handled by the Department of Clinical Biochemistry according to current guidelines. No biological material will be stored for further use.

Arterial gasses measure approx. 1mL of arterial blood, taken from the radial artery.

Other blood samples measure in 10-15 ml of venous blood, typically taken from the cubital vein.

Risks:

There are few side effects of NIV treatment:

Some people feel uncomfortable by having the mask on, as it fits tightly to the face. Some will experience dryness of the eyes, nose and mouth, because the airflow. The mask can, if not seated properly, give pressure ulcers, especially over the nose. Due the high pressure from the machine, one can get a sense of flatulence. NIV should not be used by the tendency to vomiting because of the risk of aspiration and patients are thoroughly instructed orally and in writing to use the NIV in a semi-sitting position (45 degrees).

Risks of blood samples are minimal and limited to the risk of hematoma at the injection site.

There are no other risks in the study. Budget

The following expenses are expected:

PhD scholarship: DKK 1,156,977 Employment of a nurse in each center who work ¼ of the time on the project in its first year and 1/8 of the time in other years: DKK 750,000 Transportation of patients and home care nurses: DKK 230,000 Thus a total of DKK 2,136,977 NIV equipment sponsored by Philips: Synchrony sets, masks, hoses and SIM cards. In total approx. 3,500,000 DKK Gentofte Hospital's Pulmonary Medicine Department. Y stands behind the idea and the protocol behind the studio.

Philips has paid for the delivered NIV devices, masks and tubing for a total of nearly 3,500,000 Danish Kroner. In addition, Philips is neither involved in the study of design or performance adaptation.

Nobody involved physicians paid by Philips or have interests in the company. Schedule January 2011 to 1 in March. 2011: Final protocol February 2011: Case Record File, informed consent forms and patient information leaflet developed.

1 April 2011:. Submission of application to the Ethics Committee, Data Protection

1 September 2011: All applications approved August 2011: First meeting of board of studies (a medical doctor (MD) and a nurse (RN) from each of all five study centers, an extra nurse from Gentofte, Kim Mikkelsen, MD (statistical consultant), Lars Henriksen and Annette Mørck (Philips), Kasper Ankjærgaard (Ph: D.student, MD), Torgny Wilcke, Philip Tonnesen ie a total of 17 persons).

May 2013 Start-up meeting and training seminar: 1 day in Copenhagen. March 15th 2013: First patient included. March 15th 2014: The last patient included. March 15th 2015: The last patient's last follow-up. April 15th 2015: Cleaned database is locked. May 2015: Results are presented at the end of the study session for the Board of Studies.

June 2015: The first manuscript draft. July 2015: Final manuscript ready and released, including poster presentations

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01513655

Contacts
Contact: Philip Tønnesen, MDSc +45 21279858 phtoe@geh.regionh.dk
Contact: Kasper L Ankjærgaard, MD +45 29922755 ankjaergaard@live.dk

Locations
Denmark
Dept. of Pulmonary Medicine Y, UH Gentofte Recruiting
Hellerup, Denmark, DK-2900
Contact: Philip Tønnesen, dr.med.sci    +45 21279858    phtoe@geh.regionh.dk   
Contact: Kasper L Ankjærgaard, MD    +45 29922755    ankjaergaard@live.dk   
Dept. of Internal Medicine O, UH Herlev Not yet recruiting
Herlev, Denmark, DK-2730
Contact: Lars C Laursen, dr.med.sci    +45 38 68 38 68    lachla01@heh.regionh.dk   
Dept. of Pulmonary Medicine and Infectional Medicine, UH Hillerød Not yet recruiting
Hillerød, Denmark, DK-3400
Contact: Ide Steffensen, MD, Ph.d    +45 4829 6581    idste@hih.regionh.dk   
Dept. of Pulmonary Medicine and Cardiology, UH Hvidovre Not yet recruiting
Hvidovre, Denmark, DK-2650
Contact: Ejvind Frausing, MD    +45 38 62 22 53    ejvind.frausing@hvh.regionh.dk   
Dept. of Pulmonary Medicine, L, UH Bispebjerg Not yet recruiting
København NV, Denmark, DK-2400
Contact: Birgitte Nybo Jensen, MD, dr.med,sci    +45 35312748    bjen0067@bbh.regionh.dk   
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Philips Respironics
Investigators
Study Chair: Philip Tønnesen, MDSc Chair of dept., Dept. of Pulmonary Medicine, UH Gentofte
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kasper Linde Ankjaergaard, MD, MD. ph.d-student, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01513655     History of Changes
Other Study ID Numbers: 2011-004866-13
Study First Received: January 16, 2012
Last Updated: December 4, 2014
Health Authority: Denmark: Ethics Committee
Denmark: Danish Dataprotection Agency

Keywords provided by University Hospital, Gentofte, Copenhagen:
COPD
Home NIV
NIV

Additional relevant MeSH terms:
Hypoventilation
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Insufficiency
Lung Diseases
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Signs and Symptoms, Respiratory

ClinicalTrials.gov processed this record on April 23, 2015