Pilot Study on the Usefulness of 3,4-diaminopyridine in the Treatment of Botulism

Botulism Clinical Trial

Official title:

Pilot Study on the Usefulness of 3,4-diaminopyridine in the Treatment of Botulism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01441557
• Other study ID #: PI11-PR-DUPONT
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 26, 2011
• Last updated: April 27, 2016
• Start date: September 2011
• Est. completion date: March 2012

Study information

• Verified date: April 2016
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: March 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• botulism

• ventilation

Exclusion Criteria:

• renal failure

• cardiac failure

• pregnancy

• under age 18

• hepatic failure

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Botulism

Intervention

Drug:
• 3,4-diaminopyridine
test dose 10 mg then 20 mg, then depending on tolerance and efficacy full-dose administration(from 10mg /8h to 20 mg /8h)

Locations

Country	Name	City	State
France	CHU	Amiens

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire, Amiens

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	electrophysiological	Primary endpoint: Clinical, electrophysiological and respiratory before and after administration of 3,4-diaminopyridine.	90 min	No