Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive (DYVINE)

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

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.

Study Overview

• Status: Unknown
• Conditions: Respiratory Insufficiency; Myopathy; Muscular Weakness
• Intervention / Treatment: Device: Bilevel pressure ventilator

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 Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Garches, France, 92380
    • Home ventilation unit and intensive care, centre of neuromuscular disease (Garches Mondor Necker Hendaye), Raymond Poincaré hospital Versailles Saint Quentin University.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Man or woman of age ≥ 18 years
• Preliminary medical examination
• Enlightened and written consent

• Genetically proved Steinert disease

  1. 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
  2. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients having a complication (number of non expected hospitalization or death) at 5 years.	Rate of patients having a complication (number of non expected hospitalization or death) at 5 years.	5 YEARS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of survival between the randomisation at 5 years	Distribution of survival between the randomisation at 5 years	5 YEARS
Number of patients having a formal indication of ventilation	Number of patients having a formal indication of ventilation	5 YEARS
Number of tracheostomized patients at 5 years	Number of tracheostomized patients at 5 years	5 YEARS
Number of non expected hospitalizations at 5 years	Number of non expected hospitalizations at 5 years	5 YEARS
Observance of the ventilation defined by an average minimal use of 4 am by 12:00 pm .	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).	5 YEARS
Degree of respiratory and sleep impairment at 5 years	Degree of respiratory and sleep impairment at 5 years	5 YEARS
Quality of life SF36, scales of depression	Quality of life SF36, scales of depression	5 YEARS

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Association Française contre les Myopathies (AFM), Paris
• Investigators: Principal Investigator: DAVID ORLIKOWSKI, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: October 20, 2010
• First Submitted That Met QC Criteria: October 20, 2010
• First Posted (Estimate): October 21, 2010

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Home ventilation; Myotonic dystrophy type 1 (DM1)
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Neurologic Manifestations; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Muscular Disorders, Atrophic; Heredodegenerative Disorders, Nervous System; Muscular Dystrophies; Myotonic Disorders; Muscle Weakness; Respiratory Insufficiency; Myotonic Dystrophy
• Other Study ID Numbers: P081221; 2009-A01023-54 (IDRCB) (Other Identifier: AFSSAPS)