DYVINE: Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Unknown status

CT.gov ID

NCT01225614

Collaborator

Association Française contre les Myopathies (AFM), Paris (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multicenter randomized controlled open labeled study testing efficacy and tolerance of early launching of night non invasive ventilation in patients with myotonic dystrophy type 1(DM1). The object of this project is to estimate the effects of the early introduction of non invasive ventilation on the arisen of complication (non expected hospitalization, tracheostomy even death) with regard to a simple respiratory follow-up in patients affected by myotonic dystrophy.

Condition or Disease	Intervention/Treatment	Phase
Myopathy Muscular Weakness Respiratory Insufficiency	Device: Bilevel pressure ventilator	Phase 3

Detailed Description

DM1 is the most frequent genetic myopathy in the adult. Actually there is no curative treatment, and symptomatic cares are essentials. The respiratory impairment is the main cause of morbid-mortality at these patients. The median of survival of the patients affected by DM1 with respiratory failure is of 59 years. Mechanisms of disease are complex implying a central and a direct impairment of respiratory muscles. These patients can present an alveolar hypoventilation, notably during night, not correlated to the muscular weakness. These patients often present a cognitive impairment complicating the interpretation of the clinical symptoms and their compliance to treatments. International recommendations for launching mechanical ventilation in neuromuscular diseases are the presence: 1) at least a clinical sign of alveolar hypoventilation, and one of the following criteria 2) diurnal hypercapnia (> 45 mmHg), 3) restrictive syndrome (vital capacity < 50 % and\or maximal inspiratory pressure < 60 cmH20), 4) the existence of a oxygen night-desaturation (SaO2 < 88 %) of more than 5 minutes. However, a Cochrane meta analyzes underline the absence of randomised study estimating the profit risk in the long term of the night-mechanical ventilation for progressive myopathies such as the DM1. The validity of these criteria and the effect of the ventilation on the survival and the complications were never estimated in DM1. On a retrospective series, the compliance is inferior and the observance is only 20 % a year and the incidence of the complications (death or resort to a tracheostomy) was 6 times as important in non observant patients.

Objective (s) of the clinical study To estimate the efficiency and the tolerance of long term night-non invasive mechanical ventilation in patients affected by DM1.

Main judgment criteria:

Mortality and non programmed hospitalization.

Experimental plan:

Multicenter, national, randomized, controlled, study on 2 parallel groups. The subjects presenting a theoretical indication following consensual criteria of ventilation will be randomized either for a start up of ventilation or for an annual monitoring.

Hypothesis: Early starting of non invasive ventilation allows a reduction of 20 % of the mortality or the number of non-programmed hospitalization compared to the control group for which the rate would be 40 %.

Study Design

Study Type:

Interventional

Actual Enrollment :

77 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive Ventilation in Adults With Myotonic Dystrophy Type 1(DM1)

Actual Study Start Date :

Oct 1, 2010

Anticipated Primary Completion Date :

Jul 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bipap ventilation	Device: Bilevel pressure ventilator Nocturnal home ventilation
Active Comparator: Standard care Standard care and ventilation if occurrence of absolute criteria of ventilation (cf infra).	Device: Bilevel pressure ventilator Nocturnal home ventilation

Arm

Intervention/Treatment

Experimental: bipap ventilation

Device: Bilevel pressure ventilator

Nocturnal home ventilation

Active Comparator: Standard care

Standard care and ventilation if occurrence of absolute criteria of ventilation (cf infra).

Device: Bilevel pressure ventilator

Nocturnal home ventilation

Outcome Measures

Primary Outcome Measures

Rate of patients having a complication (number of non expected hospitalization or death) at 5 years. [5 YEARS]
Rate of patients having a complication (number of non expected hospitalization or death) at 5 years.

Secondary Outcome Measures

Distribution of survival between the randomisation at 5 years [5 YEARS]
Distribution of survival between the randomisation at 5 years
Number of patients having a formal indication of ventilation [5 YEARS]
Number of patients having a formal indication of ventilation
Number of tracheostomized patients at 5 years [5 YEARS]
Number of tracheostomized patients at 5 years
Number of non expected hospitalizations at 5 years [5 YEARS]
Number of non expected hospitalizations at 5 years
Observance of the ventilation defined by an average minimal use of 4 am by 12:00 pm . [5 YEARS]
Observance of the ventilation defined by an average minimal use of 4 am by 12:00 pm (determined in a objective way by the counter of the device).
Degree of respiratory and sleep impairment at 5 years [5 YEARS]
Degree of respiratory and sleep impairment at 5 years
Quality of life SF36, scales of depression [5 YEARS]
Quality of life SF36, scales of depression

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Man or woman of age ≥ 18 years
Preliminary medical examination
Enlightened and written consent
Genetically proved Steinert disease

Presenting at least one of the following 3 criteria

A hypercapnia: PaCO2 > 45 mmHg or
A night-desaturation: SaO2 < 88 % more than consecutive 5 minutes or
Apnea syndrome with significant sleep:index of apnea / hypopnea> a 30 / hour

And with presence of at least a clinical sign: dyspnoea, orthopnea, headaches, asthenia, diurnal sleepiness, or any other sign suggestive of disturbance of the sleep or of respiratory dysfunction

Exclusion Criteria:

Age inferior to 18
Regime of legal protection
Pregnancy
Absolute indication for ventilation: clinical signs (dyspnoea, orthopnea, headaches, asthenia, diurnal sleepiness), AND PaCO2 > 60 mmHg, AND night-desaturation < 88 % AND one CV < 50 % of the theoretical or the PIMAX < 60 cm H2O
Acute respiratory failure
Already ventilated patient
Patient under oxygen
Not (beneficiary to a regime of Social Security or legal successor)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Home ventilation unit and intensive care, centre of neuromuscular disease (Garches Mondor Necker Hendaye), Raymond Poincaré hospital Versailles Saint Quentin University.	Garches		France	92380