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

A

Assistance Publique - Hôpitaux de Paris

Status and phase

Unknown
Phase 3

Conditions

Myopathy
Respiratory Insufficiency
Muscular Weakness

Treatments

Device: Bilevel pressure ventilator

Study type

Interventional

Funder types

Other

Identifiers

NCT01225614
P081221
2009-A01023-54 (IDRCB) (Other Identifier)

Details and patient eligibility

About

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.

Full 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 %.

Enrollment

77 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

77 participants in 2 patient groups

bipap ventilation
Experimental group
Treatment:
Device: Bilevel pressure ventilator
Standard care
Active Comparator group
Description:
Standard care and ventilation if occurrence of absolute criteria of ventilation (cf infra).
Treatment:
Device: Bilevel pressure ventilator

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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