Phase 3, multi-center, randomized, two-arm, parallel, double blinded, active controlled for non-inferiority evaluation of efficacy and safety of snake anti-venom produced by Padra Serum Alborz in comparison with snake anti-venom produced by Razi Vaccine and Serum Research Institute in snakebite victims.
Evaluation of efficacy and safety of anti-venom produced by Padra Serum Alborz
Design
An active controlled, parallel group, double blinded, randomized clinical trial
Settings and conduct
The study is double blinded, multi-center in Mashhad, Ahvaz, Shiraz and Uromia. victims will be receiving the intervention treatments randomly after inclusion /exclusion evaluation and signing of inform consent form. Quantity of required antivenoms based on physical examination, para-clinic tests and physicians diagnosis will be prepared for injection by nurse and will be infused. thirty minutes, 1, 6, 12, 48 and 72 hours after injection victims will be visited by physician and everything will be recorded in eCRF. After discharge of victim from hospital, serum sickness questioner through phone call one and two weeks after antivenom administration will be asked.
Participants/Inclusion and exclusion criteria
Inclusion criteria:
Iranian Victims of 2- 60 years of age with snake bite, signed Informed consent,
hospital entrance within 12 hours of snake bite and indication of antivenom administration.
Exclusion criteria:
Victims with history of allergy to horse serum, history of snake bite or scorpion sting, presence of two or more numbers of bites, sea snakebite, received antivenom prior to reach to study center, Having chronic disease.
Intervention groups
Intervention group 1: Anti-venom of Padra Serum Alborz (Vial).
Intervention group 2: Anti-venom of Razi (Ampule)
Main outcome variables
Stopping progression of swelling and neurotoxicity symptoms, Normalized coagulation abnormalities till 48 hours.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20180515039672N2
Registration date:2020-02-19, 1398/11/30
Registration timing:prospective
Last update:2020-02-19, 1398/11/30
Update count:1
Registration date
2020-02-19, 1398/11/30
Registrant information
Name
Maryam Amini Pouya
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8889 6696
Email address
maryam.aminipooya@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-02-20, 1398/12/01
Expected recruitment end date
2020-06-20, 1399/03/31
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Phase 3, multi-center, randomized, two-arm, parallel, double blinded, active controlled for non-inferiority evaluation of efficacy and safety of snake anti-venom produced by Padra Serum Alborz in comparison with snake anti-venom produced by Razi Vaccine and Serum Research Institute in snakebite victims.
Public title
Phase 3, multi-center clinical trial for evaluation of two types of snake anti-venom
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
History of snakebite
Informed consent for participating in the study
Men or Women victims with age of 2 to 60 years
Victims who arrive at mentioned hospitals within 12 hours after snakebite
Victims who need anti-venom according to the bite severity scale
Victims who have Iranian nationality (having national ID)
Exclusion criteria:
Victims with history of allergy to horse serum
Victims who have experience of prior treatment with snake or scorpion antivenom due to snakebite or scorpion sting in the past.
Victims with two or more number of bites on arrival at hospital.
Victims who already have received antivenom prior to reach to hospital.
Victims who do wound manipulation (incision, suction, burning and so on) before hospital entrance.
Victims with life threatening bleeding (such as bleeding in mouth and upper respiratory tract)
Victims who receive heparin and warfarin
Victims with history of coagulopathy, cardiac disease, neuromuscular disease, kidney and liver failure.
Pregnant or breastfeeding women.
Victims who have sea snakebite.
Victims who need for mechanical ventilation at the time of registration.
Age
From 2 years old to 60 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Outcome assessor
Data analyser
Sample size
Target sample size:
98
Randomization (investigator's opinion)
Randomized
Randomization description
Randomization sequences have been made online using the quadruple blocks for the total sample size of 98 victims (ratio of 1:1).
The produced randomization sequences would be located in the study site. Each randomization code have been already labeled on each related anti-venom (2 groups of intervention) and be presented in the study site drug stock.
After assurance of victim eligibility and receiving the informed consent, according to the randomization sequence, the specific anti-venom would be injected to victims.
Blinding (investigator's opinion)
Double blinded
Blinding description
All victims after meeting the eligibility criteria are examined by physician. After allocating of randomization code to each victim, the nurse with using the drug stock in the study site (with the research tag on them) prepare the infusion bag for Intravenous infusion.
Due to identical appearance of infusion bags and administration process, none of the victims would be aware of the group of intervention. It is tried to minimize the awareness of physician from the type of intervention but it's unavoidable. Importance of blindness is emphasized while education the nurses and physicians.
In addition since the data are documented in eCRF as untitled codes, the data management team would receive the information without the identification of victims. Therefore, the blindness in victims and outcome assessor team would be obtained completely and for physician would be partial.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Mashhad University of Medical Sciences
Street address
Shahid Fakouri Blvd.
City
Mashhad
Province
Razavi Khorasan
Postal code
9138813944
Approval date
2020-01-18, 1398/10/28
Ethics committee reference number
IR.MUMS.REC.1398.295
Health conditions studied
1
Description of health condition studied
Snake-Bite
ICD-10 code
T63.0
ICD-10 code description
Toxic effect of snake venom
Primary outcomes
1
Description
Percentage of victims with improving in snakebite symptoms
Timepoint
At baseline and 48 hours after antivenom administration
Method of measurement
A) Stopping progression of swelling B) Normalized coagulation abnormalities C) Stopping the progression of neurotoxicity
Secondary outcomes
1
Description
Percentage of adverse events
Timepoint
0.5, 1, 6, 12, 24, 48, 72 hours, 7 and 14 days after Intervention
Method of measurement
Reporting the incidence proportion
2
Description
dose of antivenom administrated
Timepoint
0.5, 1, 6, 12, 24, 48, 72 hours after Intervention
Method of measurement
Number of injected vials
Intervention groups
1
Description
Intervention group: Vial containing 10 mL of sterile solution of snake antivenom produced by Padra Serum Alborz which each mL is able to neutralize more than 50 LD50. Initial dose: Moderate or severe signs and symptoms, 5 and 10 vials, respectively; Repeat dose: 1 to 6 hours after initial dose, 5 vials until symptom treatment or administration of totally 20 vials; Maintenance dose: 2 vials Infusion every 6 hours up to 3 doses.
Category
Treatment - Drugs
2
Description
Control group: Ampules containing 10 mL of sterile solution of snake antivenom produced by Razi Vaccine and Serum Research Institute which each mL is able to neutralize more than 50 LD50. Initial dose: Moderate or severe signs and symptoms, 5 and 10 ampules, respectively; Repeat dose: 1 to 6 hours after initial dose, 5 ampules until symptom treatment or administration of totally 20 vials; Maintenance dose: 2 ampules Infusion every 6 hours up to 3 doses.