Clinical trial NCT03326492: Evaluation of Anti-venoms Serum in Africa
Official title: Evaluation of Anti-venoms Serum in Africa (ESAA). Data Collection in Real Life Conditions
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Snake Bites
Antivenins
Snake Venoms
Keywords: Snake bites
Antivenom serum
Snake venoms
Lead sponsor: Institut Pasteur
Sponsor class: INDUSTRY
Collaborators: name: Cameroon Society of Epidemiology (CaSE)
name: Centre International de Recherches d'Enseignements et de Soins (CIRES)
name: Centre Pasteur du Cameroun
name: Inosan Biopharma
First posted: 2017-10-31
Enrollment: 474
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any patient over 5 years old (inclusive) visiting at a participating center for curative care following a snake bite, with or without confirmed envenoming, will be proposed to participate in the study

Brief summary: There is little or no assessment under real-use conditions of the efficacy and the tolerance in the short, medium and long term of the antivenoms currently on the market and used in the treatment of snake bites.

The main objective is to assess the short term tolerance (\< 2 hours post-injection) of the antivenom Inoserp Pan-Africa® (temporary market authorization) from Inosan laboratory currently available in Cameroon.

Detailed description: Globally, the number of annual envenomings is estimated to be between 420,000 and 1,800,000. In sub-Saharan Africa, the annual number of envenomings is estimated at 315,000, leading to more than 9,000 amputations and about 7,000 deaths.

Snake bites are recognized by many authors as a neglected disease, whose incidence is underestimated or even unknown in several countries of sub-Saharan Africa. Few data are currently available on the morbidity, mortality and economic impact of snake bites.

In Cameroon and particularly in the northern part of the country, where the density of snakes is high, a few studies have been carried out. In 2002, the annual incidence of envenomings was estimated at 200/100 000 inhabitants, of which 85% was due to Echis ocellatus, and the lethality was 23.9% in some centers. The Ministry of Public Health introduced snake bites in 2015 as a priority health problem in the list of diseases being monitored. Thus, a national epidemiological surveillance system, with a weekly count of snake bites, has been implemented. In the first year, the incidence of annual snake bites was 11.4/100,000 inhabitants, representing more than 2,500 bites per year, including 43 deaths and a case fatality rate of up to 6% in some areas. The northern region (Adamaoua, North and Far North regions) (savanna and mixed zone) accounts for 40% of the country's burden and 77% of the deadly burden, while the forest zone accounts for 32% of the burden Morbid disease and 16% of the fatal burden (ministerial source). The monitoring is based on paper registers for bite reporting, supplemented by the sending of pharmacovigilance data by text messages, but this is very little used in current practice. The data collection system in Cameroon could therefore be improved in terms of both completeness and speed of centralizing data.

These estimates are likely to be well below the reality given the non-exhaustive nature of the data collection and the frequent use of traditional practitioners without referral in a hospital structure.

In recent years, FAV-Afrique® produced by Sanofi-Pasteur was the treatment of reference for venomous snake bites in West and Central Africa. It was the most evaluated and the most effective, reducing by a factor 5 to 10 the mortality. This anti-venom serum was polyspecific, containing an antivenom against ten species of snakes: Naja melanoleuca, nigricollis \& haje; Dendroaspis polylepis, viridis \& jamesoni, Bitis gabonica \& arietans; Echis leucogaster \& ocellatus.

However, Sanofi-Pasteur stopped production (last batch produced in January 2014 and expired in June 2016), making it necessary to use other snake antivenoms. Since the end of 2015, two new antivenoms are available in Cameroon where they are granted a provisional marketing authorization. Few clinical trials have evaluated the antivenoms currently available in Africa.

Some clinical efficacy and safety data have been published for Inoserp Pan-Africa®. However, the number of subjects was limited and assessment was limited to the period of hospitalization.

The lack of sufficient data on incidence and mortality associated with snake bites, the current weakness of the epidemiological data collection system and the presence on the market of antivenoms that are very little evaluated in terms of tolerance, effectiveness make action necessary.

The main objective of the study is therefore to assess the tolerance and the efficacy of the antivenom Inoserp Pan-Africa® from Inosan laboratory currently available in Cameroon.This study will be conducted under routine conditions in order to avoid bias in the results through the implementation of dedicated logistics which would not be representative of the usual conditions.

Eligibility criteria: Inclusion Criteria:

* Any patient over 5 years old (inclusive) visiting at a participating center for a snake bite with or without confirmed envenoming
* Informed consent to research

Exclusion Criteria:

* Patient refusal
* Under 5 year-old
* Antivenom serum administration before the arrival in the participating center
* History of severe allergic reactions to antivenom serum

Primary outcomes:
measure: Short term tolerance of the antivenom serum Inoserp Pan-Africa®
timeFrame: 30 months
Secondary outcomes:
measure: Short term efficacy of the antivenom serum Inoserp Pan-Africa®
timeFrame: 30 months
measure: Medium term tolerance of the antivenom serum Inoserp Pan-Africa®
timeFrame: 30 months
measure: Medium term efficacy of the antivenom serum Inoserp Pan-Africa®
timeFrame: 30 months
Other outcomes:
Locations:
city: Akonolinga
country: Cameroon
facility: Hôpital de District d'Akonolinga
city: Buea
country: Cameroon
facility: Hôpital régional de Buea
city: Guider
country: Cameroon
facility: Hôpital de District de Guider
city: Kolofata
country: Cameroon
facility: Hôpital de District de Kolofata
city: Limbe
country: Cameroon
facility: Hôpital Régional de Limbe
city: Mora
country: Cameroon
facility: Hôpital de District de Mora
city: N'Gaoundéré
country: Cameroon
facility: Hôpital Norvégien de N'Gaoundéré
city: N'Gaoundéré
country: Cameroon
facility: Hôpital Régional de N'Gaoundéré
city: Njombé
country: Cameroon
facility: Hôpital Saint Malte de Njombe
city: Poli
country: Cameroon
facility: Hôpital de District de Poli
city: Sa'a
country: Cameroon
facility: Hôpital de District de Sa'a
city: Tokombere
country: Cameroon
facility: Hôpital de District de Tokombere
city: Yaoundé
country: Cameroon
facility: Centre des Urgences de Yaounde (CURY)
Study officials:
affiliation: Cameroon Society of Epidemiology, Cameroon
name: Armand Nkwescheu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Médecins Sans Frontière
name: Yap Boum, MD
role: PRINCIPAL_INVESTIGATOR
References: