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. 2025 Apr 30;26(1):144.
doi: 10.1186/s13063-025-08841-7.

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

Sara Domínguez-Rodríguez  1   2 , David Lora  3   4   5 , Alfredo Tagarro  3   6   7 , Cinta Moraleda  3   8 , Álvaro Ballesteros  3 , Lola Madrid  3   9 , Lilit Manukyan  3 , Olivier Marcy  10 , Valeriane Leroy  11 , Alessandra Nardone  12 , David Burger  13 , Quique Bassat  14   15   16   17   18 , Matthew Bates  19 , Raoul Moh  20 , Pui-Ying Iroh Tam  21   22 , Tisungane Mvalo  23 , Justina Magallhaes  17 , W Chris Buck  24   25 , Jahit Sacarlal  25 , Victor Mussime  26   27 , Chishala Chabala  28 , Hilda Angela Mujuru  29 , Pablo Rojo  4   8   30 ; EMPIRICAL group
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Statistical analysis plan for the "empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia" clinical trial

Sara Domínguez-Rodríguez et al. Trials. .

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.

Keywords: Child mortality; Cytomegalovirus; Empirical; Factorial; Factorial randomized clinical trial; HIV; Infants; Pneumonia; Statistical analysis plan; Tuberculosis; Valganciclovir.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The trial has been approved by the Investigation Ethics Committee of Medicines (CEIm) N°CEIm: 19/096 Hospital 12 de Octubre on March 13, 2019, and by all the enrolling sites’ ethical boards and regulatory agencies. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study flow diagram template for the EMPIRICAL trial (based on the CONSORT flow diagram). HIV, human immunodeficiency virus; TB-T, tuberculosis treatment; Val, valganciclovir; SoC, standard of care; TB, tuberculosis; Hb, hemoglobin
Fig. 2
Fig. 2
Kaplan–Meier survival estimates at day 15 and day 360 among the randomization arms
Fig. 3
Fig. 3
Survival estimates (hazard ratios) of the factorial analysis
Fig. 4
Fig. 4
Volcano plot of the serious adverse events risk difference for each treatment
See this image and copyright information in PMC

References

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