Statistical analysis plan for the “empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia” clinical trial

Abstract Background The EMPIRICAL trial aims to assess safety and efficacy of an empirical treatment against cytomegalovirus (CMV) and tuberculosis (TB) compared to standard of care (SoC), on adverse events and 15-day and 1-year mortality among infants living with HIV hospitalized with severe pneumo...

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Main Authors: Sara Domínguez-Rodríguez, David Lora, Alfredo Tagarro, Cinta Moraleda, Álvaro Ballesteros, Lola Madrid, Lilit Manukyan, Olivier Marcy, Valeriane Leroy, Alessandra Nardone, David Burger, Quique Bassat, Matthew Bates, Raoul Moh, Pui-Ying Iroh Tam, Tisungane Mvalo, Justina Magallhaes, W. Chris Buck, Jahit Sacarlal, Victor Mussime, Chishala Chabala, Hilda Angela Mujuru, Pablo Rojo, on behalf of EMPIRICAL group
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Trials
Subjects:
Online Access:https://doi.org/10.1186/s13063-025-08841-7
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author Sara Domínguez-Rodríguez
David Lora
Alfredo Tagarro
Cinta Moraleda
Álvaro Ballesteros
Lola Madrid
Lilit Manukyan
Olivier Marcy
Valeriane Leroy
Alessandra Nardone
David Burger
Quique Bassat
Matthew Bates
Raoul Moh
Pui-Ying Iroh Tam
Tisungane Mvalo
Justina Magallhaes
W. Chris Buck
Jahit Sacarlal
Victor Mussime
Chishala Chabala
Hilda Angela Mujuru
Pablo Rojo
on behalf of EMPIRICAL group
author_facet Sara Domínguez-Rodríguez
David Lora
Alfredo Tagarro
Cinta Moraleda
Álvaro Ballesteros
Lola Madrid
Lilit Manukyan
Olivier Marcy
Valeriane Leroy
Alessandra Nardone
David Burger
Quique Bassat
Matthew Bates
Raoul Moh
Pui-Ying Iroh Tam
Tisungane Mvalo
Justina Magallhaes
W. Chris Buck
Jahit Sacarlal
Victor Mussime
Chishala Chabala
Hilda Angela Mujuru
Pablo Rojo
on behalf of EMPIRICAL group
author_sort Sara Domínguez-Rodríguez
collection DOAJ
description Abstract Background The EMPIRICAL trial aims to assess safety and efficacy of an empirical treatment against cytomegalovirus (CMV) and tuberculosis (TB) compared to standard of care (SoC), on adverse events and 15-day and 1-year mortality among infants living with HIV hospitalized with severe pneumonia in Africa. Methods and design The EMPIRICAL trial (NCT03915366) is an international multicenter phase II-III, open-label randomized factorial clinical trial conducted in six African countries. The trial has four randomization arms in a 1:1:1:1 fashion with patients allocated to (i) TB-Treatment plus SoC, (ii) valganciclovir plus SoC, (iii) both TB-Treatment and valganciclovir plus SoC, and (iv) SoC only. Discussion This paper describes the statistical analysis plan (SAP) for the trial which, per the study publication plan, needs to be published prior to the database lock and final analysis results. The SAP includes details of the analyses to be undertaken and unpopulated tables that will be reported to address primary and secondary endpoints. The database will be locked on 31st January 2025. Trial registration ClinicalTrials.gov: NCT03915366 (registered on April 16, 2019), Universal Trial Number: U111-1231–4736, Pan African Clinical Trial Registry: PACTR201994797961340.
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spelling doaj-art-d39f0ca9be634810a5697b14162b3fef2025-08-20T02:11:11ZengBMCTrials1745-62152025-04-0126111310.1186/s13063-025-08841-7Statistical analysis plan for the “empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia” clinical trialSara Domínguez-Rodríguez0David Lora1Alfredo Tagarro2Cinta Moraleda3Álvaro Ballesteros4Lola Madrid5Lilit Manukyan6Olivier Marcy7Valeriane Leroy8Alessandra Nardone9David Burger10Quique Bassat11Matthew Bates12Raoul Moh13Pui-Ying Iroh Tam14Tisungane Mvalo15Justina Magallhaes16W. Chris Buck17Jahit Sacarlal18Victor Mussime19Chishala Chabala20Hilda Angela Mujuru21Pablo Rojo22on behalf of EMPIRICAL groupInstituto de Investigación Sanitaria Hospital (imas12), Fundación Biomedica del Hospital Universitario (FIB-H12O)Instituto de Investigación Sanitaria Hospital (imas12), Fundación Biomedica del Hospital Universitario (FIB-H12O)Instituto de Investigación Sanitaria Hospital (imas12), Fundación Biomedica del Hospital Universitario (FIB-H12O)Instituto de Investigación Sanitaria Hospital (imas12), Fundación Biomedica del Hospital Universitario (FIB-H12O)Instituto de Investigación Sanitaria Hospital (imas12), Fundación Biomedica del Hospital Universitario (FIB-H12O)Instituto de Investigación Sanitaria Hospital (imas12), Fundación Biomedica del Hospital Universitario (FIB-H12O)Instituto de Investigación Sanitaria Hospital (imas12), Fundación Biomedica del Hospital Universitario (FIB-H12O)Université de Bordeaux, Bordeaux Population Health, GHiGSInstitut National de La Santé Et de La Recherche Médicale (Inserm), CERPOPPenta-Onlus Foundation (PENTA)Stichting Katholieke Universiteit—Radboudumc (RUMC)ISGlobal, Hospital Clínic, Universitat de BarcelonaUniversity of LincolnUnité Pédagogique de Dermatologie Et Infectiologie, UFR Sciences Médicales, Programme PAC-CI, Ivory CoastKamuzu University Health SciencesLilongwe Medical Relief Trust (LMRFT), UNC Project MalawiCentro de Investigação Em Saúde de Manhiça (CISM)David Geffen School of Medicine, University of California Los AngelesUniversidade Eduardo Mondlane (UEM)Department of Paediatrics and Child Health, College of Health Sciences, Makerere UniversitySchool of Medicine, University of ZambiaUniversity of ZimbabweSpanish Clinical Research Network (SCReN)Abstract Background The EMPIRICAL trial aims to assess safety and efficacy of an empirical treatment against cytomegalovirus (CMV) and tuberculosis (TB) compared to standard of care (SoC), on adverse events and 15-day and 1-year mortality among infants living with HIV hospitalized with severe pneumonia in Africa. Methods and design The EMPIRICAL trial (NCT03915366) is an international multicenter phase II-III, open-label randomized factorial clinical trial conducted in six African countries. The trial has four randomization arms in a 1:1:1:1 fashion with patients allocated to (i) TB-Treatment plus SoC, (ii) valganciclovir plus SoC, (iii) both TB-Treatment and valganciclovir plus SoC, and (iv) SoC only. Discussion This paper describes the statistical analysis plan (SAP) for the trial which, per the study publication plan, needs to be published prior to the database lock and final analysis results. The SAP includes details of the analyses to be undertaken and unpopulated tables that will be reported to address primary and secondary endpoints. The database will be locked on 31st January 2025. Trial registration ClinicalTrials.gov: NCT03915366 (registered on April 16, 2019), Universal Trial Number: U111-1231–4736, Pan African Clinical Trial Registry: PACTR201994797961340.https://doi.org/10.1186/s13063-025-08841-7Statistical analysis planChild mortalityCytomegalovirusEmpiricalFactorialFactorial randomized clinical trial
spellingShingle Sara Domínguez-Rodríguez
David Lora
Alfredo Tagarro
Cinta Moraleda
Álvaro Ballesteros
Lola Madrid
Lilit Manukyan
Olivier Marcy
Valeriane Leroy
Alessandra Nardone
David Burger
Quique Bassat
Matthew Bates
Raoul Moh
Pui-Ying Iroh Tam
Tisungane Mvalo
Justina Magallhaes
W. Chris Buck
Jahit Sacarlal
Victor Mussime
Chishala Chabala
Hilda Angela Mujuru
Pablo Rojo
on behalf of EMPIRICAL group
Statistical analysis plan for the “empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia” clinical trial
Trials
Statistical analysis plan
Child mortality
Cytomegalovirus
Empirical
Factorial
Factorial randomized clinical trial
title Statistical analysis plan for the “empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia” clinical trial
title_full Statistical analysis plan for the “empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia” clinical trial
title_fullStr Statistical analysis plan for the “empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia” clinical trial
title_full_unstemmed Statistical analysis plan for the “empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia” clinical trial
title_short Statistical analysis plan for the “empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia” clinical trial
title_sort statistical analysis plan for the empirical treatment against cytomegalovirus and tuberculosis in hiv infected infants with severe pneumonia clinical trial
topic Statistical analysis plan
Child mortality
Cytomegalovirus
Empirical
Factorial
Factorial randomized clinical trial
url https://doi.org/10.1186/s13063-025-08841-7
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