PARASOL: Diaphragm Paralysis: Surgery or Mechanical Ventialion
Study Details
Study Description
Brief Summary
Summary Rationale: The diaphragm is a dome-shaped muscle which separates the thoracic cavity from the abdomen. In patients with diaphragm paralysis the treatment (surgery versus non-invasive ventilation) is based on physician preference, not sound scientific evidence. Clearly studies are needed to guide a scientific decision making.
Objective: In this pilot study the investigators will evaluate if participants are willing and able to participate in a randomized trial. Secondly this pilot study is also needed to know the clinical relevant effect of both therapies on EQ-5D_5L, the latter being the primary outcome. Finally, it will show the investigators the costs of both therapies form a societal perspective.
Study design: open-label, multi center randomized controlled trial / pilot Study population:
20 participants >18 year and diagnosed with a unilateral of bilateral diaphragm paralysis resulting from phrenic nerve injury.
Intervention: 10 participants for surgical plication and 10 participants for nocturnal non-invasive ventilation.
Main study parameters/endpoints: The primary question is whether the intended cost effectiveness / cost utility study is feasible. In the investigators opinion the intended study is feasible if at least 50% of the participants fulfilling the inclusions criteria are randomized in this pilot study.
The second goal of the preparatory study is to describe the effect of both plication and NIV on the endpoints of the intended efficiency study. The intended primary endpoint is quality of life as measured by the EQ-5D-5L questionnaire. Secondary endpoints are; the Medical Research Council (MRC) dyspnoea scale, the Diaphragmatic Paralysis Questionnaire, Borg dyspnoea score, Endurance Shuttle Walk Test (ESWT), spirometry in both sitting and supine position, a polysomnography and transcutaneous measurement of carbon dioxide an oxygen saturation at night.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
INTRODUCTION AND RATIONALE
The diaphragm is a dome-shaped muscle which separates the thoracic cavity from the abdomen. It is the most important muscle of respiration innervated by the phrenic nerves. While many diseases might interfere with its function (1), in the intended study the investigators will focus on diaphragm paralysis due to phrenic nerve injury. Two types of diaphragm paralysis can be distinguished: unilateral and bilateral. Patients with unilateral paralysis perceive exertional dyspnea, have an impaired exercise capacity and orthopnea.(2) Patients with a bilateral paralysis usually have more symptoms and might even develop respiratory failure. (3) In addition, all patients with a diaphragm paralysis may have poor sleep quality, as the diaphragm is the only active respiratory muscle during REM sleep. (4) Currently, two treatment approaches for patients with diaphragm paralysis are used in clinical practice: surgical diaphragm plication and nocturnal non-invasive ventilation (NIV). Plication is a minimal invasive surgical procedure that aims to stiffen the diaphragm and such limits dysfunctional (paradoxical movement) excursions of the paralytic diaphragm. The procedure is performed in ±70 patients per year in the Netherlands. NIV is a non-invasive mode of positive pressure ventilatory assistance; through a facial mask the ventilator supports patient breathing effort. Patients with diaphragm paralysis use their ventilator mainly during night time, to improve quality of sleep and such to reduce day time symptoms. In the Netherlands, home mechanical ventilation is very well organized, as care is delivered by only 4 specialized centers. NIV for diaphragm paralysis is started in around 50 patients yearly.
Currently, both plication and nocturnal NIV appear beneficial and both options are covered by health care insurance. However, it is unknown which intervention is most beneficial from a patient perspective. For instance, comparison on patient relevant outcome measures and complications between these treatment approaches is unknown. In addition, patients with diaphragm paralysis may develop severe symptoms, limiting daily activities including ability to perform their professional work. To assess the overall impact of this a detailed cost analysis is necessary to compare both treatments from a societal perspective. A solid cost effectiveness / cost utility study will reveal which therapy is the best option from a societal perspective.
This preparatory study will be set up as a randomized pilot study to evaluate if patients are willing and able to participate in this trial. Question is, are participants willing to participate, are they willing to travel to the other institute and are they able to comply with the follow-up measurements. Participants referred to either one of the therapies might be biased towards that therapy and the questions is whether well informed about both therapies, they are willing to participate. To know what clinical effect of both therapies is relevant the EQ-5D-5L is used. It is unknown whether there is a significant difference on the outcome between both therapies. A search in trial registries did not reveal any study with similar research questions. Based on the outcomes of this preparatory study a power analysis can be performed for the seminal study. Due to the acute origin of a diaphragm paralysis patients get suddenly severely impaired which is interfering enormously with their lives. As this is often happening in middle aged patients they often have to discontinue professional activities. This means that the potential impact of this disorder is huge from patient and societal perspective and needs to be assessed.
As both therapies are completely different for invasiveness, the investigators need to compare the side effects and possible complications. Possible complications of the surgery are infection, bleeding and abdominal pain while the well know side effects of ventilatory support are leakage of the mask, aerophagia and a-synchrony between breathing pattern of the patient and the ventilator. As this is also an important outcome of this pilot study participants will be closely monitored from the start of therapy and there will be a telephone call after 2 months
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Surgical plication Surgical plication of the diaphragm |
Other: surgical plication" or "nocturnal non-invasive ventilation
10 participants for surgical plication and 10 participants for nocturnal non-invasive ventilation.
|
| Active Comparator: Mechanical ventilation Non-invasive ventiatilatory support |
Other: surgical plication" or "nocturnal non-invasive ventilation
10 participants for surgical plication and 10 participants for nocturnal non-invasive ventilation.
|
Outcome Measures
Primary Outcome Measures
- The primary question is whether a randomized trial comparing surgery versus non-invasive ventilation is feasible. [0-15 months]
The study is feasible if at least 50% of the patients fulfilling the inclusion criteria are randomized in this pilot study, number of participants in study, 20
- Change in EuorQOL 5 Dimensions 5 Level (EQ-5D-5L questionnaire) range 1-1-1-1-1 (best score) to 5-5-5-5-5 (worst score) [baseline and 6 months]
questionnaire to score QUALY
Eligibility Criteria
Criteria
Inclusion Criteria:
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18 years
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diagnosed with a unilateral or bilateral diaphragm paralysis based on isolated phrenic nerve injury.
Unilateral or bilateral diaphragm paralysis is defined as follows: complaints of dyspnea and / or orthopnea combined with a drop in VC of more than 15% when change from upright to supine position and a positive sniff test during fluoroscopy or ultrasonography. A positive sniff test means that the diaphragm stands still or even moves in cranial direction (paradoxical movement ) during the sniff inspiratory maneuver.
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Ability to provide written consent
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Time between diagnosis and treatment should be at least 1 year
Exclusion Criteria:
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Patients diagnosed with a unilateral or bilateral diaphragm paralysis due to a more systemic neurological or neuromuscular disorder like for example Amyotrophic Lateral Sclerosis ,
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Hypercapnia during daytime (PaCO2 > 6.0 kPa)
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Radiotherapy of the thorax
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Contra indication for diaphragm surgery.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University Medical Center Groningen
- ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 80-87700-98-22188