Botulism Clinical Trial
Official title:
Pilot Study on the Usefulness of 3,4-diaminopyridine in the Treatment of Botulism
Main objectives:
Evaluate the effectiveness of an administration of 3,4-diaminopyridine (FIRDAPSE ®) in
severe botulinic poisoning in measuring the effect on electrophysiological and respiratory
parameters
Secondary Objective:
Study the natural history of electrophysiological and respiratory parameters during the
botulinic intoxication
Primary endpoint:
Clinical, electrophysiological and respiratory before and after administration of
3,4-diaminopyridine.
Study Design:
Pilot study, prospective, interventional.
Study population:
Case series (n = 8 patients) suffering from botulinic type A, respiratory failure, but with
no other organ failure
Experimental treatment :
3,4-diaminopyridine, FIRDAPSE ® (BioMarin) The dosage will be gradually increased according
to a predetermined scheme and will not exceed 60 mg / day and 20 mg / dose.
Statistics:
Intra-individual comparison of physiological parameters measured before and after
administration of 3,4-diaminopyridine. Electromyographic and respiratory parameters will be
measured for each patient. Then a dose of 10 mg of 3,4-diaminopyridine will be
administrated. If this dose is well tolerated and provides a relative improvement of 10% for
at least one of the parameters studied, the dose will be maintained at 10 mg for 48 hours 3
times a day then increased to 20 mg.
The primary endpoint is the change in the amplitude of muscle response evaluated by the
subtraction of amplitude at T1.5 and T0.
Main objectives:
Evaluate the effectiveness of an administration of 3,4-diaminopyridine (FIRDAPSE ®) in
severe botulinic poisoning in measuring the effect on electrophysiological and respiratory
parameters
Secondary Objective:
Study the natural history of electrophysiological and respiratory parameters during the
botulinic intoxication
Primary endpoint:
Clinical, electrophysiological and respiratory before and after administration of
3,4-diaminopyridine.
Study Design:
Pilot study, prospective, interventional.
Study population:
Case series (n = 8 patients) suffering from botulinic type A, respiratory failure, but with
no other organ failure
Experimental treatment :
3,4-diaminopyridine, FIRDAPSE ® (BioMarin) The dosage will be gradually increased according
to a predetermined scheme and will not exceed 60 mg / day and 20 mg / dose.
Statistics:
Intra-individual comparison of physiological parameters measured before and after
administration of 3,4-diaminopyridine. Electromyographic and respiratory parameters will be
measured for each patient. Then a dose of 10 mg of 3,4-diaminopyridine will be
administrated. If this dose is well tolerated and provides a relative improvement of 10% for
at least one of the parameters studied, the dose will be maintained at 10 mg for 48 hours 3
times a day then increased to 20 mg.
The primary endpoint is the change in the amplitude of muscle response evaluated by the
subtraction of amplitude at T1.5 and T0.
Quantitative variables are expressed as mean ± standard deviation or median (minimum -
maximum) and qualitative variables as percentages.
The null hypothesis (the evolution is identical between the two doses) will be rejected in
favour of the alternative hypothesis (the evolution is different) using the mixed model
analysis of variance on the threshold of 5% for the first kind with adjusting the amplitude
at T0, age, the time between patient admission and the first administration of
3,4-diaminopyridine. The evolution of latency and respiratory parameters will be analyzed
with the same mixed ANOVA without risk adjustment alpha.
For the secondary objective, the evolution curves of the amplitude of muscle response on the
one hand and respiratory function on the other hand, will be built for each patient.
The mean (or median) of amplitude and respiratory function at weaning will be calculated
with a confidence level of 95% (or range). The average time between the first
3,4-diaminopyridine administration and withdrawal of mechanical ventilation will also be
calculated.
For each dose, the average evolution of the amplitude will be calculated with a confidence
level of 95%.
Statistical analysis will be carried out using SAS software version 9.2.
;
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
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