PMID- 34972765
OWN - NLM
STAT- MEDLINE
DCOM- 20220307
LR  - 20220307
IS  - 2044-6055 (Electronic)
IS  - 2044-6055 (Linking)
VI  - 11
IP  - 12
DP  - 2021 Dec 31
TI  - New chemotherapy regimens and biomarkers for Chagas disease: the rationale and 
      design of the TESEO study, an open-label, randomised, prospective, phase-2 
      clinical trial in the Plurinational State of Bolivia.
PG  - e052897
LID - 10.1136/bmjopen-2021-052897 [doi]
LID - e052897
AB  - INTRODUCTION: Chagas disease (CD) affects ~7 million people worldwide. 
      Benznidazole (BZN) and nifurtimox (NFX) are the only approved drugs for CD 
      chemotherapy. Although both drugs are highly effective in acute and paediatric 
      infections, their efficacy in adults with chronic CD (CCD) is lower and variable. 
      Moreover, the high incidence of adverse events (AEs) with both drugs has hampered 
      their widespread use. Trials in CCD adults showed that quantitative PCR (qPCR) 
      assays remain negative for 12 months after standard-of-care (SoC) BZN treatment 
      in ~80% patients. BZN pharmacokinetic data and the nonsynchronous nature of the 
      proliferative mammal-dwelling parasite stage suggested that a lower BZN/NFX 
      dosing frequency, combined with standard or extended treatment duration, might 
      have the same or better efficacy than either drug SoC, with fewer AEs. METHODS 
      AND ANALYSIS: New ThErapies and Biomarkers for ChagaS infEctiOn (TESEO) is an 
      open-label, randomised, prospective, phase-2 clinical trial, with six treatment 
      arms (75 patients/arm, 450 patients). Primary objectives are to compare the 
      safety and efficacy of two new proposed chemotherapy regimens of BZN and NFX in 
      adults with CCD with the current SoC for BZN and NFX, evaluated by qPCR and 
      biomarkers for 36 months posttreatment and correlated with CD conventional 
      serology. Recruitment of patients was initiated on 18 December 2019 and on 20 May 
      2021, 450 patients (study goal) were randomised among the six treatment arms. The 
      treatment phase was finalised on 18 August 2021. Secondary objectives include 
      evaluation of population pharmacokinetics of both drugs in all treatment arms, 
      the incidence of AEs, and parasite genotyping. ETHICS AND DISSEMINATION: The 
      TESEO study was approved by the National Institutes of Health (NIH), U.S. Food 
      and Drug Administration (FDA), federal regulatory agency of the Plurinational 
      State of Bolivia and the Ethics Committees of the participating institutions. The 
      results will be disseminated via publications in peer-reviewed journals, 
      conferences and reports to the NIH, FDA and participating institutions. TRIAL 
      REGISTRATION NUMBER: NCT03981523.
CI  - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Alonso-Vega, Cristina
AU  - Alonso-Vega C
AD  - Barcelona Institute for Global Health (ISGLOBAL), Barcelona, Spain.
FAU - Urbina, Julio A
AU  - Urbina JA
AUID- ORCID: 0000-0003-0736-0378
AD  - Center for Biochemistry and Biophysics, Venezuelan Institute for Scientific 
      Research (IVIC), Caracas, Distrito Capital, Venezuela, Bolivarian Republic of.
FAU - Sanz, Sergi
AU  - Sanz S
AD  - Biostatistics and Data Management Unit, Barcelona Institute for Global Health, 
      Barcelona, Spain.
AD  - Consorcio de Investigacion Biomedica en Red de Epidemiologia y Salud Publica 
      (CIBERESP), Madrid, Spain.
AD  - Department of Basic Clinical Practice, Universitat de Barcelona, Barcelona, 
      Spain.
FAU - Pinazo, Maria-Jesus
AU  - Pinazo MJ
AD  - Barcelona Institute for Global Health (ISGLOBAL), Barcelona, Spain.
AD  - CIBER de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
FAU - Pinto, Jimy Jose
AU  - Pinto JJ
AUID- ORCID: 0000-0002-6884-4379
AD  - Fundacion Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio 
      Ambiente (CEADES), Cochabamba, Bolivia, Plurinational State of.
FAU - Gonzalez, Virginia R
AU  - Gonzalez VR
AD  - Department of Biological Sciences, The University of Texas at El Paso, El Paso, 
      Texas, USA.
FAU - Rojas, Gimena
AU  - Rojas G
AD  - Fundacion Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio 
      Ambiente (CEADES), Cochabamba, Bolivia, Plurinational State of.
FAU - Ortiz, Lourdes
AU  - Ortiz L
AD  - Fundacion Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio 
      Ambiente (CEADES), Tarija, Bolivia, Plurinational State of.
AD  - Universidad Autonoma Juan Misael Saracho, Tarija, Bolivia, Plurinational State 
      of.
FAU - Garcia, Wilson
AU  - Garcia W
AD  - Centro Plataforma Chagas Sucre, Fundacion Ciencia y Estudios Aplicados para el 
      Desarrollo en Salud y Medio Ambiente (CEADES), Sucre, Bolivia, Plurinational 
      State of.
AD  - Programa Departamental de Chagas Chuquisaca, Servicio Departamental de Salud de 
      Chuquisaca, Chuquisaca, Bolivia, Plurinational State of.
FAU - Lozano, Daniel
AU  - Lozano D
AD  - Fundacion Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio 
      Ambiente (CEADES), Cochabamba, Bolivia, Plurinational State of.
FAU - Soy, Dolors
AU  - Soy D
AD  - Pharmacy Service, Division of Medicines, Hospital Clinic de Barcelona, Barcelona, 
      Spain.
AD  - Institut de Investigacio Biomedica Agusti Pi i Sunyer (IDIBAPS), Universitat de 
      Barcelona, Barcelona, Spain.
FAU - Maldonado, Rosa A
AU  - Maldonado RA
AD  - Department of Biological Sciences, The University of Texas at El Paso, El Paso, 
      Texas, USA.
FAU - Nagarkatti, Rana
AU  - Nagarkatti R
AD  - Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics 
      Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, 
      Maryland, USA.
FAU - Debrabant, Alain
AU  - Debrabant A
AD  - Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics 
      Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, 
      Maryland, USA.
FAU - Schijman, Alejandro
AU  - Schijman A
AD  - Laboratorio de Biologia Molecular de la Enfermedad de Chagas, Instituto de 
      Investigaciones en Ingenieria Genetica y Biologia Molecular, Buenos Aires, 
      Argentina.
AD  - National Scientific and Technical Research Council (CONICET), Buenos Aires, 
      Argentina.
FAU - Thomas, M Carmen
AU  - Thomas MC
AD  - Consejo Superior de Investigaciones Cientificas, Instituto de Parasitologia y 
      Biomedicina Lopez-Neyra, Granada, Spain.
FAU - Lopez, Manuel Carlos
AU  - Lopez MC
AD  - Consejo Superior de Investigaciones Cientificas, Instituto de Parasitologia y 
      Biomedicina Lopez-Neyra, Granada, Spain.
FAU - Michael, Katja
AU  - Michael K
AD  - Department of Chemistry and Biochemistry, The University of Texas at El Paso, El 
      Paso, Texas, USA.
FAU - Ribeiro, Isabela
AU  - Ribeiro I
AD  - Dynamic Portfolio Unit, Drugs for Neglected Diseases initiative, Geneva, 
      Switzerland.
FAU - Gascon, Joaquim
AU  - Gascon J
AD  - Barcelona Institute for Global Health (ISGLOBAL), Barcelona, Spain.
AD  - CIBER de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
FAU - Torrico, Faustino
AU  - Torrico F
AD  - Fundacion Ciencia y Estudios Aplicados para el Desarrollo en Salud y Medio 
      Ambiente (CEADES), Cochabamba, Bolivia, Plurinational State of.
FAU - Almeida, Igor C
AU  - Almeida IC
AUID- ORCID: 0000-0002-2443-8213
AD  - Department of Biological Sciences, The University of Texas at El Paso, El Paso, 
      Texas, USA icalmeida@utep.edu.
LA  - eng
SI  - ClinicalTrials.gov/NCT03981523
GR  - U01 AI129783/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20211231
PL  - England
TA  - BMJ Open
JT  - BMJ open
JID - 101552874
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Biomarkers
MH  - Bolivia
MH  - *Chagas Disease/drug therapy
MH  - Child
MH  - Humans
MH  - Prospective Studies
MH  - Treatment Outcome
PMC - PMC8720984
OTO - NOTNLM
OT  - chemotherapy
OT  - immunology
OT  - microbiology
OT  - parasitology
OT  - tropical medicine
COIS- Competing interests: The TESEO study principal investigators declare no financial 
      and competing interests for the overall trial and each study site.
EDAT- 2022/01/02 06:00
MHDA- 2022/03/08 06:00
PMCR- 2021/12/31
CRDT- 2022/01/01 05:18
PHST- 2022/01/01 05:18 [entrez]
PHST- 2022/01/02 06:00 [pubmed]
PHST- 2022/03/08 06:00 [medline]
PHST- 2021/12/31 00:00 [pmc-release]
AID - bmjopen-2021-052897 [pii]
AID - 10.1136/bmjopen-2021-052897 [doi]
PST - epublish
SO  - BMJ Open. 2021 Dec 31;11(12):e052897. doi: 10.1136/bmjopen-2021-052897.