Clinical trial NCT00560287: Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
Official title: Role of Non-invasive Ventilation in Amyotrophic Lateral Sclerosis: Volume Versus Pressure Mode
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Amyotrophic Lateral Sclerosis
Chronic Respiratory Failure
Keywords: Amyotrophic Lateral Sclerosis
Non-invasive ventilation
Chronic Respiratory Failure
Lead sponsor: Fondazione Salvatore Maugeri
Sponsor class: OTHER
First posted: 2007-11-19
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Non-invasive mechanical ventilation (NIV) has been increasingly used as a treatment of chronic hypercapnic respiratory failure. Its use in patients affected by chronic obstructive pulmonary disorders is still controversial, while most of the studies performed in restrictive thoracic disorders (RTD), and in particular in neuromuscular patients, suggested alleviation of the symptoms of chronic hypoventilation in the short term, and in two small studies survival was prolonged.

In the terminal phase of the disease, when the respiratory muscles became weaker it is very likely that the operators need to frequently adjust the level of inspiratory pressure in an attempt to guarantee an adequate tidal volume, so that alveolar hypoventilation may be avoided.

Theoretically the use of a volume assisted ventilation may overpass this problem of frequent variations of the settings, since the provision of a fixed tidal volume may always guarantee and adequate alveolar ventilation.

The primary aims of this multicenter randomized study are to evaluate the clinical efficacy, the patients' tolerance and quality of life and the frequency of changing settings in a group of patients with SLS and initial chronic respiratory failure undergoing long-term NIV with Pressure Support Ventilation or Volume Assisted Ventilation.

Detailed description: Background

Non-invasive mechanical ventilation (NIV) has been increasingly used as a treatment of chronic hypercapnic respiratory failure. Its use in patients affected by chronic obstructive pulmonary disorders is still controversial, while most of the studies performed in restrictive thoracic disorders (RTD), and in particular in neuromuscular patients, suggested alleviation of the symptoms of chronic hypoventilation in the short term, and in two small studies survival was prolonged. As a matter of fact a recent Cochrane review stated that "long-term mechanical ventilation should be offered as a therapeutic option to patients with chronic respiratory failure due to neuromuscular diseases". Recurrent episodes of nocturnal desaturation especially during REM sleep may deeply influence the prognosis of patients affect by these disorders (i.e. ALS), and they are often associated with hypercapnia, so that the correction of nocturnal hypoventilation seems to be the major goal to achieve with the ventilatory treatment.

A very recent randomized controlled trial show that in ALS without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life, including sleep quality. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy, like riluzole.

Most of the studies performed in RTD disorders were performed using a pressure assisted mode (i.e Pressure Support Ventilation), because of the supposed better tolerance of the patients and easy of settings for the operators, even though this has never been scientifically proven.

In the terminal phase of the disease, when the respiratory muscles became weaker it is very likely that the operators need to frequently adjust the level of inspiratory pressure in an attempt to guarantee an adequate tidal volume, so that alveolar hypoventilation may be avoided.

Theoretically the use of a volume assisted ventilation may overpass this problem of frequent variations of the settings, since the provision of a fixed tidal volume may always guarantee and adequate alveolar ventilation.

The primary aims of this multicenter randomized study are to evaluate the clinical efficacy, the patients' tolerance and quality of life and the frequency of changing settings in a group of patients with SLS and initial chronic respiratory failure undergoing long-term NIV with Pressure Support Ventilation or Volume Assisted Ventilation.

Aim of the Project

The primary aims of the project are to evaluate the clinical efficacy, the patients' tolerance and quality of life and the frequency of changing settings in a group of patients with SLS and initial chronic respiratory failure undergoing long-term NIV with Pressure Support Ventilation or Volume Assisted Ventilation.

• Enrollment criteria: Patients with the diagnosis of ALS and one of the following signs: 1) Vital Capacity \< 50% predicted 2) a Maximal Inspiratory Pressure (MIP) \< 60% predicted 3) polygraphic signs of nocturnal hypoventilation with daytime symptoms.

- The patients will be randomized to receive NIV with one of the following modes: 1) Pressure Support Ventilation with the inspiratory pressure set according to the patient's tolerance in order to achieve an expired tidal volume \> 6 ml/Kg and \<8ml/Kg. The back-up rate will be set at 10 breaths/min. 2) Volume assist ventilation with a back-up rate of 10 breaths/min and a tidal volume set to achieve an expired tidal volume \> 6 ml/Kg and \<8ml/Kg

Eligibility criteria: Inclusion Criteria:

* Patients with the diagnosis of ALS and one of the following signs:

  * Vital Capacity \< 50% predicted
  * A Maximal Inspiratory Pressure (MIP) \< 60% predicted
  * Polygraphic signs of nocturnal hypoventilation with daytime symptoms.

Exclusion Criteria:

* Life expectancy\>12 months
* Any comorbidity
* Acute Respiratory Failure

Primary outcomes:
measure: quality of life
timeFrame: 1 year
measure: tolerance to NIV
timeFrame: 1 year
measure: number of hours of NIV per day
timeFrame: 1 year
measure: frequency of hospital admission
timeFrame: 1 year
measure: frequency of changing the ventilator settings by the operator.
timeFrame: 1 year
Secondary outcomes:
measure: survival
timeFrame: 1 year
measure: diurnal and nocturnal gas exchange
timeFrame: 1 year
measure: Pulmonary Function Tests (PFTs).
timeFrame: 1 year
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Fondazione S.Maugeri
city: Pavia
country: Italy
facility: Respiratory Unit FSM
Study officials:
affiliation: Fondazione Salvatore Maugeri
name: Stefano Nava
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione S.maugeri
name: Stefano Nava, MD
role: PRINCIPAL_INVESTIGATOR
References: