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Nifurtimox versus benznidazole or placebo for asymptomatic Trypanosoma cruzi infection (Equivalence of Usual Interventions for Trypanosomiasis - EQUITY): Study protocol for a randomised controlled trial
- Source :
- Repositorio EdocUR-U. Rosario, Universidad del Rosario, instacron:Universidad del Rosario, Trials, Trials, Vol 20, Iss 1, Pp 1-10 (2019)
- Publication Year :
- 2019
- Publisher :
- BioMed Central Ltd., 2019.
-
Abstract
- Background Either benznidazole (BZN) or nifurtimox (NFX) is recommended as equivalent to treat Trypanosoma cruzi infection. Nonetheless, supportive data from randomised trials is limited to individuals treated with BZN in southern cone countries of Latin America. Methods The goal of this randomised, concealed, blind, parallel-group trial is to inform the trypanocidal efficacy and safety of NFX and its equivalence to BZN among individuals with T. cruzi positive serology (TC+). Eligible individuals are TC+, 20–65 years old, with no apparent symptoms/signs or uncontrolled risk factors for cardiomyopathy and at negligible risk of re-infection. Consenting individuals (adherent to a 10-day placebo run-in phase) receive a 120-day BID blinded treatment with NFX, BZN or matching placebo (2:2:1 ratio). The four active medication arms include (1) a randomly allocated sequence of 60-day, conventional-dose (60CD) regimes (BZN 300 mg/day or NFX 480 mg/day, ratio 1:1), followed or preceded by a 60-day placebo treatment, or (2) 120-day half-dose (120HD) regimes (BZN 150 mg/day or NFX 240 mg/day, ratio 1:1). The primary efficacy outcome is the proportion of participants testing positive at least once for up to three polymerase chain reaction (PCR) assays (1 + PCR) 12–18 months after randomisation. A composite safety outcome includes moderate to severe adverse reactions, consistent blood marker abnormalities or treatment abandons. The trial outside Colombia (expected to recruit at least 60% of participants) is pragmatic; it may be open-label and not include all treatment groups, but it must adhere to the randomisation and data administration system and guarantee a blinded efficacy outcome evaluation. Our main comparisons include NFX groups with placebo (for superiority), NFX versus BZN groups and 60CD versus 120HD groups (for non-inferiority) and testing for the agent-dose and group-region interactions. Assuming a 1 + PCR ≥ 75% in the placebo group, up to 25% among BZN-treated and an absolute difference of up to ≥ 25% with NFX to claim its trypanocidal effect, 60–80 participants per group (at least 300 from Colombia) are needed to test our hypotheses (80–90% power; one-sided alpha level 1%). Discussion The EQUITY trial will inform the trypanocidal effect and equivalence of nitroderivative agents NFX and BZN, particularly outside southern cone countries. Its results may challenge current recommendations and inform choices for these agents. Trial registration ClinicalTrials.gov, NCT02369978. Registered on 24 February 2015. Electronic supplementary material The online version of this article (10.1186/s13063-019-3423-3) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
Pediatrics
Chagas disease
Time Factors
Chagas disese
Medicine (miscellaneous)
Neuropathic pain
Skin manifestation
Time factor
law.invention
Efficacy
Nitroimidazole derivative
Study Protocol
Randomized controlled trial
Randomized controlled trial (topic)
law
Multicenter Studies as Topic
Pharmacology (medical)
Multicenter studies as topic
Treatment outcome
Drug safety
Middle aged
1102 Cardiorespiratory Medicine and Haematology
Randomized Controlled Trials as Topic
lcsh:R5-920
biology
Headache
Therapeutic equivalency
Middle Aged
Trypanocidal Agents
Multicenter study
Polymerase chain reaction
Treatment Outcome
Serology
Benznidazole
Nitroimidazoles
Female
medicine.symptom
lcsh:Medicine (General)
medicine.drug
Human
Adult
medicine.medical_specialty
Trypanosoma cruzi
Treatment refusal
Major clinical study
Antitrypanosomal agent
Colombia
Placebo
Asymptomatic
Article
Treatment duration
Adverse outcome
Young Adult
Randomized controlled trials as topic
Trypanosomiasis
General & Internal Medicine
parasitic diseases
Trypanocidal agents
medicine
Pathogenicity
Humans
Chagas Disease
Paresthesia
Dyspepsia
Nifurtimox
Therapeutic equivalence
Disease severity
Aged
business.industry
Medication compliance
Time factors
Correction
1103 Clinical Sciences
medicine.disease
biology.organism_classification
Asymptomatic diseases
Multicenter study (topic)
Therapy effect
Drug effect
Drug efficacy
Young adult
Therapeutic Equivalency
Cardiovascular System & Hematology
Asymptomatic Diseases
Asymptomatic disease
Parasitology
business
Controlled study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Repositorio EdocUR-U. Rosario, Universidad del Rosario, instacron:Universidad del Rosario, Trials, Trials, Vol 20, Iss 1, Pp 1-10 (2019)
- Accession number :
- edsair.doi.dedup.....2c9524fffce18b4429909ec7ca8413c1