Meta AnalysisID 4362
固醇14-脱甲基酶抑制剂在克氏锥虫感染动物模型中的作用
CRD42021205000
What is the effect of sterol 14-demethylase Inhibitors in animal models of Trypanosoma cruzi infection? Context and rationale Chagas disease is a severe illness caused by Trypanosoma cruzi, a hemoflagellated protozoan. U
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Record Fields
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- Meta Analysis Id
- 4362
- Evidence Id
- 12920
- Core Evidence Id
- 12920
- Source Meta Analysis Id
- 4328
- Herb2 Meta Analysis Id
- HBMA004328
- Crd Id
- CRD42021205000
- Title
- The effect of sterol 14-demethylase inhibitors in animal models of Trypanosoma cruzi infection
- Review Question
- What is the effect of sterol 14-demethylase Inhibitors in animal models of Trypanosoma cruzi infection? Context and rationale Chagas disease is a severe illness caused by Trypanosoma cruzi, a hemoflagellated protozoan. Up to date, only nifurtimox (NFX) and benznidazole (BZ) are currently available for treatment. Drug repurposing arose as a simple, faster, and cost-benefit strategy to identify new therapeutic options. Initially developed for systemic mycosis, sterol 14-demethylase inhibitors emerged as promissory compounds in both in vitro and in vivo models of T. cruzi infection, showing an apparent parasitemia clearance and a parasitological cure. The repurposed compounds posaconazole and ravuconazole were moved forward to clinical trials in different populations and stages of the disease. The overall conclusion in all clinical studies was that BZ was more effective than azoles, with less proportion of positive qPCR in blood. These results were unexpected in light of the results of the animal studies referred to above. Considering the therapeutic failure, new approaches were proposed to assess compound efficacy, concluding that sterol 14-demethylase inhibitors were more likely to arrest the infection in a parasitostatic manner. We hypothesized that preclinical studies with triazoles in T. cruzi experimental models were not sufficiently interpreted within their logical scope and limitations, partially explaining clinical studies' failure. We will perform a systematic review (and a meta-analysis, if possible) to determine the effect of sterol 14-demethylase inhibitors in animal models with T. cruzi infection. We will try to determine if the clinical failure could be anticipated if such analysis had been carried out before moving the candidate compounds to clinical research.
- Study Type Included
- Inclusion criteria: Controlled studies with a separate control group (infected non treated group). Exclusion criteria: Studies without a separate control group (infected non treated group).
- Condition Being Studied
- Participant
- Animal
- Inclusion criteria: Any mammal models for acute and/or chronic infection experimentally infected. Exclusion criteria: In vitro infection models; non-mammal experimental models; natural infection.
- Human Disease Modelled
- American Trypanosomiasis (Chagas disease).
- Intervention
- Inclusion criteria: Studies will be included if they assess the efficacy of a sterol 14-demethylase inhibitor on parasitemia, survival and/or cure rates in an in vivo experimental T. cruzi infection. Exclusion criteria: Papers will be excluded if the sterol 14-demethylase inhibitor was administered in combination with any other drug unless data from monotherapy treatment is reported.
- Comparator Control
- Inclusion criteria: Infected non treated and/or infected and treated with benznidazole or nifurtimox Exclusion criteria: Any other evaluated compound.
- Main Outcome
- Outcome Measure
- Inclusion criteria: Parasitemia, survival and/or cure rates. Exclusion criteria: Other secondary measures.
- Additional Outcome
- Study Method
- Keyword
- 14-alpha Demethylase Inhibitors; Animals; Chagas Disease; Models, Animal; Sterol 14-Demethylase
- Contact
- Ernesto Gulin [email protected]
- Organisational Affiliation
- Instituto de Investigaciones Biomédicas (INBIOMED) UBA-CONICET. https://www.fmed.uba.ar/inbiomed/informacion-general
- Funding Source
- No funding.
- Other Selection Criteria
- Inclusion criteria: No language or year of publication restriction will be applied. If necessary, papers in languages other than English were translated by scientific translators. Exclusion criteria: Not an original paper (e.g., review or letter to the editor), duplicated publication; in case a paper occurred more than one time in one of the databases, only one retrieval will be included.
- Final Publication
- Same Topic Review
- Published Protocol
- Review Type
- Pre-clinical animal intervention review
- Language
- Spanish
- Country
- Argentina
- Review Stage
- Review Ongoing
- First Submission Date
- 2021-08-12
- Registration Date
- 2021-12-13
- Anticipated Start Date
- 2021-03-01
- Anticipated Completion Date
- 2021-12-31
- Title Cn
- 固醇14-脱甲基酶抑制剂在克氏锥虫感染动物模型中的作用
- Title En
- The effect of sterol 14-demethylase inhibitors in animal models of Trypanosoma cruzi infection
- Bilingual Status
- complete