Trial document




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  DRKS00007977

Trial Description

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Title

Impact of High-Intensity-NPPV on cardiac and pulmonary function in stable hypercapnic COPD

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Chronic Obstructive Pulmonary Disease (COPD) is a very prevalent disease worldwide. It might progress towards a stage in which the lungs are not capable anymore to deliver enough oxygen but also not to remove the excess carbon dioxide from the blood. At this stage, patients are ventilatory insufficient. Mechanical ventilation through a mouth and/or nose mask (so called non-invasive ventilation) can help ventilatory insufficient patients to improve this situation. Studies have shown clear benefits of this strategy once respiratory insufficiency occurs during an acute deterioration of the disease for example during an infection. However, benefits have been long less clear for patients who are ventilatory insufficient in stable state, i.e. without any other objective factor at that moment leading to deterioration except than their disease. Last years, the idea has become popular that no benefits were found was merely a consequence of the use of too low inspiratory pressures and too low frequencies delivered by the ventilator (low intensity non-invasive ventilation). With the use of higher pressures and higher breathing frequencies (high-intensity non-invasive ventilation) better outcomes on gas exchange but also outcomes more relevant to the patients were obtained.
However, there remain some gaps and concerns about this strategy. First, other factors than improvement in gas exchange might be important to improve patient-centred outcomes, such as improvement in lung function or function of the respiratory muscles. Secondly, concerns have been raised that the use of too high pressures is of disadvantageous for the heart, especially in patients who already have a heart disease. Therefore, the present study is designed to compare high intensity ventilation with low-intensity ventilation both on lung and heart function. Patients will receive non-invasive ventilation during the night with high and low-intensity each for 6 weeks in succession and will be asked how they experience the ventilation, their quality of life, and measurements will be done measuring lung function, exercise tolerance, respiratory muscle function and cardiac function.

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Brief Summary in Scientific Language

Chronic non-invasive positive pressure ventilation (NPPV) in patients with Chronic Obstructive Pulmonary Disease (COPD) has been controversial for a long time, as results from different randomised controlled trials did not show meaningful benefits. However, since a ventilatory strategy was adopted with higher pressures and higher back-up breathing frequencies (so called high-intensity NPPV) compared to the prior strategy with lower pressures and breathing frequency (low-intensity NPPV), ventilation, resultant arterial blood gases, but also patient centred outcomes improved.
So, while we now seem to realise that a certain amount of inspiratory pressure and breathing frequency is needed to achieve meaningful benefits, there are also several knowledge gaps and concerns about this strategy. First it is unknown whether the improvement in clinical outcomes as health-related quality of life and survival can be fully described to reversal of hypoventilation. Other factors such as improvement of lung mechanics, respiratory muscle function or strength, decrease in inflammation by improved ventilation might be equally important. We can use this knowledge to properly select the patients that benefit most from this very costly therapy.
Secondly, concerns have been raised about the effect of using high-intensity NPPV on cardiac function. High-Intensity NPPV leads to higher intrathoracal pressures which might influence left ventricular preload and thus output. This might be of special importance in patients who are already cardiac compromised.
The aim of the present study is to compare pulmonary and cardiac effects of high-intensity versus low intensity NPPV in patients with severe stable hypercapnic COPD. We will investigate in a randomised cross-over design both acute (directly under NPPV) and longer term effects (6 weeks). Measurements will consist of health-related quality of life questionnaires; measurements of lung function, gas exchange, exercise tolerance, breathing patterns, respiratory muscle activity and functioning; and measurements of cardiac functioning (signs of heart failure, echocardiography, blood pressure and rhythm monitoring). Primary endpoint is the cardiac output measured by echocardiography after 6 weeks of NPPV therapy.

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Organizational Data

  •   DRKS00007977
  •   2015/04/13
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  •   yes
  •   Approved
  •   43/2015, Ethik-Kommission der Universität Witten/Herdecke
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Secondary IDs

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Health Condition or Problem studied

  •   J96.1 -  Chronic respiratory failure
  •   J44 -  Other chronic obstructive pulmonary disease
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Interventions/Observational Groups

  •   The study has a cross-over design:
    The patients in arm 1 will be ventilated noninvasively (by nose or mouth/nose mask) during the night, the first 6 weeks with low-intensity settings (IPAP ≤ 14 ±3 mbar; EPAP 5±2 mbar; pressure support (PSV); respiratory rate ≤ 12±2/min)then they are switched to high-intensity settings with higher inspiratory pressures (IPAP at least 18 mbar, assist- controlled mode) and higher backup respiratory rate.
  •   Cross-over design:
    The patients in arm 2 will be ventilated noninvasively the first 6 weeks with high-intensity settings, whereafter they are switched to low-intensity settings for further 6 weeks.
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Crossover
  •   N/A
  •   N/A
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Primary Outcome

Left ventricular output during spontaneous breathing after 6 weeks of nocturnal noninvasive ventilation (Hi- or Low-NPPV) compared to the baseline left ventricualr output during spontaneous breathing. Left ventricular output is defined as stroke volume x heart rate. The stroke volume will be measured echocardiographically.

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Secondary Outcome

cardiac function under spontaneous breathing after 6 weeks of high or low-Intensity NPPV versus baseline measurements before NPPV:

echocardiac measurements:
Left ventricular ejection fraction (method of Simpson);
Right ventricular Function and Tricuspidal annular plane excursion (TAPSE);
Left ventricular output under NPPV;

Systolic and Diastolic blood pressure;
Systolic Pressure pulmonal artery;

measurements under NPPV:
Blood gas analysis;
Transcutaneous CO2 monitoring;
Respiratory muscle EMG;
Breathing pattern analysis;

lung function:
Dyspnea sensation (BORG scale);
6-minute walking test in meter;
Lung function testing (spirometry und lung volumes).

quality of life:
SRI Questionnaire

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2015/04/14
  •   12
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

COPD GOLD stage III-IV; naive for, but with an indication for NIV; clinically suspected or proven cardiac comorbidity; pH more than 7.35, signed informed consent; age more than 18.

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Exclusion Criteria

Last hospitalisation for an exacerbation less than one month before inclusion; age under 18; deafness; mental retardation; inability to sign informed consent form

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Lungenklinik Köln-MerheimKliniken der Stadt Köln gGmbH
    • Mr.  Prof. Dr. med.  Wolfram  Windisch 
    • Ostmerheimer Strasse 200
    • 51109  Köln
    • Germany
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    • Lungenklinik Köln-MerheimKliniken der Stadt Köln gGmbH
    • Mr.  Prof. Dr. med.  Wolfram  Windisch 
    • Ostmerheimer Strasse 200
    • 51109  Köln
    • Germany
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    • Lungenklinik Köln-MerheimKliniken der Stadt Köln gGmbH
    • Mr.  Prof. Dr. med.  Wolfram  Windisch 
    • Ostmerheimer Strasse 200
    • 51109  Köln
    • Germany
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Sources of Monetary or Material Support

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    • Lungenklinik MerheimAbteilung PneumologieLehrstuhl für Pneumologie der Universität Witten/Herdecke
    • Mr.  Professor  Wolfram  Windisch 
    • Ostmerheimer Straße 200
    • 51109  Köln
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2016/02/08
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Trial Publications, Results and other Documents

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