Optimization of PCR Technique to Assess Parasitological Response for Patients With Chronic Chagas Disease

NCT01678599 | Completed Phase 4

• 1 other identifier: MSF/DNDi-CD-PCR-01
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to estimate the gain in sensitivity of several multiple-sample strategies of PCR samples with respect to the current standard (single sample of 10 ml) to detect Chagas chronic stage at baseline and to identify the optimal sampling strategy based on the sensitivity, cost,the completeness of sampling and the acceptability for study patients.

Conditions

Chagas Disease

Keywords

Chagas Disease; PCR; diagnosis

Outcome Measures

Primary Outcomes (2)

• The primary endpoints are: - A positive or negative PCR at baseline (BL) among serology positive patients.

  Bloods will be at baseline and EOT (last day of treatment +10 + 5 days), 6 months and 12 months follow-up visits.

• - Identification of the optimal relationship between sensitivity and feasibility at baseline.

  For BL and EOT visits, blood samples will be as follows: one initial blood of 10 mL (Sample 1), followed by 1 sample of 5mL collected immediately following (Sample 2); plus one blood sample of 10mL collected 1 week later (Sample 3). Once the optimal strategy has been defined for EOT visit (see section 10.7), this will be the strategy of blood collection to be used at the 6 and 12 months follow-up visits

  Bloods will be at baseline and EOT (last day of treatment +10 + 5 days), 6 months and 12 months follow-up visits.

Secondary Outcomes (4)

• - Identification of the optimal relationship between sensitivity and Identification of the optimal relationship between sensitivity and feasibility at End Of Treatment (EOT)

  Bloods will be at baseline and EOT (last day of treatment +10 + 5 days), 6 months and 12 months follow-up visits.

• - The proportion of patients who convert from PCR (+) at baseline to PCR (-) at EOT - to be estimated using 1) the current sampling schedule (CS), the most sensitive one and the optimal one.

  Bloods will be at baseline and EOT (last day of treatment +10 + 5 days), 6 months and 12 months follow-up visits.

• - The proportion of patients who convert from PCR (+) at baseline to PCR (-) at 6 and 12 months follow-up - to be estimated using 1) the current sampling schedule (CS) and the optimal one (based on EOT data).

  Bloods will be at baseline and EOT (last day of treatment +10 + 5 days), 6 months and 12 months follow-up visits.

• - Relative reduction [(parasite count at baseline - parasite count at EOT, 6 and 12 months)/parasite count at baseline] of parasitemia - to be evaluated through parasite load at EOT, 6 and 12 months through quantitative PCR.

  Bloods will be at baseline and EOT (last day of treatment +10 + 5 days), 6 months and 12 months follow-up visits.

Study Arms (1)

Benznidazol

OTHER

This is a single arm, open label study; therefore, all subjects enrolled will receive benznidazol.

Drug: Benznidazole

Interventions

Benznidazole DRUG

All patients participating in this study will be treated with Benznidazole, 5mg/Kg/day PO BID for 60 days with a maximum daily dose of 300mg, as per routine care provided by MSF in rural communities in Aiquile. For patients \> 60 kg, the total dose should be calculated (5mg/Kg x Weight x 60 days) and treatment duration should be adjusted/prolonged accordingly. This treatment is in accordance with the local recommendations from the Ministerio de Salud y Deportes de Bolivia.

Also known as: LAFEPE Benznidazol

Benznidazol

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between \> 18 - 60 years
• Diagnosis of T. cruzi infection by Chagas serology. Two out of three serological tests must be positive \[conventional ELISA, recombinant ELISA, or HAI)
• Written informed consent form

You may not qualify if:

• Women in reproductive age who have a positive pregnancy test at screening, or who are breastfeeding Note: Women in reproductive age must accept to use a contraceptive method during the entire treatment phase of the trial
• Current presentation of serious health condition such as: active pulmonary tuberculosis and clinical signs of liver or renal failure.
• Chagasic cardiomyopathy stage II, III and IV (according to the NYHA classification)
• Subjects requiring pacemaker implantation or other serious cardiac conduction defects
• History of CD treatment with benznidazole or nifurtimox at any time in the past
• Inability to comply with follow-up and/or not having a permanent address
• History of alcohol abuse or any other drug addiction

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• Medecins Sans Frontieres, Netherlands: collaborator

Study Sites (1)

Medicin Sans Frontièrs (MSF)

Aiquile, Bolivia

Location

Related Publications (2)

• Duffy T, Bisio M, Altcheh J, Burgos JM, Diez M, Levin MJ, Favaloro RR, Freilij H, Schijman AG. Accurate real-time PCR strategy for monitoring bloodstream parasitic loads in chagas disease patients. PLoS Negl Trop Dis. 2009;3(4):e419. doi: 10.1371/journal.pntd.0000419. Epub 2009 Apr 21.

  PMID: 19381287 BACKGROUND

• Parrado R, Ramirez JC, de la Barra A, Alonso-Vega C, Juiz N, Ortiz L, Illanes D, Torrico F, Gascon J, Alves F, Flevaud L, Garcia L, Schijman AG, Ribeiro I. Usefulness of Serial Blood Sampling and PCR Replicates for Treatment Monitoring of Patients with Chronic Chagas Disease. Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01191-18. doi: 10.1128/AAC.01191-18. Print 2019 Feb.

  PMID: 30509941 DERIVED

Related Links

• Drugs for Neglected Diseases initiative

MeSH Terms

Conditions

Chagas Disease; Disease

Interventions

benzonidazole

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lourdes Loza, Biochemist

  Medicin Sans Frontièrs

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2012
• First Posted: September 5, 2012
• Study Start: April 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2013
• Last Updated: June 25, 2018

Record last verified: 2018-06

Locations

BO (1)