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

April 27, 2016 updated by: Centre Hospitalier Universitaire, Amiens

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France, 80000
        • CHU

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • botulism
  • ventilation

Exclusion Criteria:

  • renal failure
  • cardiac failure
  • pregnancy
  • under age 18
  • hepatic failure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
electrophysiological
Time Frame: 90 min

Primary endpoint:

Clinical, electrophysiological and respiratory before and after administration of 3,4-diaminopyridine.
90 min

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire, Amiens

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (ACTUAL)

February 1, 2012

Study Completion (ACTUAL)

March 1, 2012

Study Registration Dates

First Submitted

September 26, 2011

First Submitted That Met QC Criteria

September 26, 2011

First Posted (ESTIMATE)

September 27, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

April 28, 2016

Last Update Submitted That Met QC Criteria

April 27, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PI11-PR-DUPONT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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