PneumoniaPhase 2/3EMPIRICALNCT03915366
Empirical Treatment Against Cytomegalovirus and Tuberculosis in HIV-infected Infants With Severe Pneumonia
A Phase 2/3 study testing Valganciclovir Oral Solution [Valcyte] and Tuberculostatic Agents in people with Pneumonia and HIV/AIDS, run by Hospital Universitario 12 de Octubre at 13 sites in 11 countries.
Trial summary
This trial will evaluate whether empirical treatment against cytomegalovirus and tuberculosis improves survival of HIV-infected infants with severe pneumonia. Read more about this study
- Who is it for?
- Ages 28 to 365 days
- Conditions the study is for
- Pneumonia, HIV/AIDS, Tuberculosis
- What is being tested?
- Valganciclovir Oral Solution [Valcyte] and Tuberculostatic Agents
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 563 participants
- Where
- 13 sitesin 11 countries
- Study dates
- 1 Mar 2020to 31 Jan 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 to 365 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 28 days to 365 days of age
- Pneumonia defined as chest indrawing or fast breathing for age, for infants 28 to 60 days of age ≥60 breaths per minute and for infants 61 to 365 days of age, ≥50 breaths per minute.
- Current hospitalization due to pneumonia with criteria for parenteral antibiotics (1 or more criteria)
- Chest indrawing with HIV infection
- No improvement with oral treatment.
- One or more danger signs according to WHO 5,44,45
Show all 17Show fewer
- Central cyanosis or saturation of O2 <90%
- Severe respiratory distress, e.g. grunting or very severe chest indrawing
- Signs of pneumonia with a general danger sign:
- Unable to drink or breastfeed
- Persisting vomiting
- Convulsions in the last 24 hours
- Lethargic or unconscious
- Stridor while calm
- Severe malnutrition
- HIV-confirmed infection (with at least one molecular method: DNA polymerase chain reaction (PCR) or RNA PCR/viral load).
- Informed consent obtained
Who cannot join
- Clinical TB (pulmonary or extrapulmonary) diagnosis, defined as the necessity of TB-T prescribed by a physician, at the moment of randomization
- Known bacteriologically confirmed TB case (at least one biological specimen positive by culture or Xpert MTB/RIF) at the moment of randomization
- Patient previously treated for TB or currently on treatment for TB
- Documented evidence of close TB exposure (household contact of a patient with documented TB during the lifetime of the child, or currently receiving TB-T)
- Pure wheezers defined as a clear clinical improvement after a bronchodilator test (give a challenge of rapid-acting inhaled bronchodilator for up to three times 15-20 minutes apart. Count the breaths and look for chest indrawing again, and then re-classify)
- Active malignancies
Show all 11Show fewer
- Systemic immunosuppressive medications. Steroids will be considered to be immunosuppressing only if >2 mg/kg of prednisone or equivalent during >15 days
- Evidence of condition other than HIV and pneumonia which precludes, to the judgment of the clinical researcher, enrollment in this trial due to risk for the patient. In case of doubt, the Trial Management Team will be contacted to assess eligibility
- Less than 2.5 kg of weight
- Hb <6 g/dL in the screening blood test or in a test done in the last 48 hours. Transfusion is permitted to achieve >6 g/dL if the patient's state allows it. In case a transfusion is administered, the patient can be enrolled
- Neutropenia <500 /mm3 in the screening blood test or in a test done in the last 48 hours. Repeating the test is allowed to check eligibility
Trial locations and contacts
13 sites in 11 countries.
13 sites in 11 countries
Mozambique2 sites
Cemtro de Investigaçao em Saúde da Manhiça
Manhiça
Hospital Central Maputo
Maputo
Malawi1 site
Malawi Liverpool Welcome Trust. Queen Elizabeth Central Hospital College of Medicine
Blantyre
Spain1 site
Fundación para la Investigación Biomédica del Hospital 12 de Octubre
Madrid, 28041
About this study
Official title: Empirical Treatment Against Cytomegalovirus and Tuberculosis in HIV-infected Infants With Severe Pneumonia: a Multicenter, Open-label Randomized Controlled Clinical Trial
This trial will evaluate whether empirical treatment against cytomegalovirus and tuberculosis improves survival of HIV-infected infants with severe pneumonia.
Read the detailed description
Pneumonia is the main cause of death in Human Immunodeficiency Virus (HIV)-infected children. A significant number of undiagnosed or poorly treated HIV-infected children present to health services with severe pneumonia. World Health Organization (WHO) guidelines to treat severe pneumonia in HIV-infected infants include empirical treatment against common bacteria plus Pneumocystis jirovecii. Although this approach has contributed to reducing overall case fatality rates, mortality in this particularly vulnerable group remains unacceptably high. Autopsy studies in Africa have shown that cytomegalovirus (CMV) infection and tuberculosis (TB) are important underdiagnosed and undertreated causes of deaths. Our objective is to evaluate whether empirical treatment against cytomegalovirus and tuberculosis improves survival of HIV-infected infants with severe pneumonia. A randomized factorial clinical trial will be conducted in six sub-Saharan African countries to evaluate the safety and efficacy of empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants aged 28 days to 365 days admitted to hospital with severe pneumonia. The primary outcome is mortality. All HIV-infected infants will receive standard of care (SoC) pneumonia treatment, including antibiotics, cotrimoxazole, and prednisolone. A group of patients will receive SoC, another group will receive valganciclovir plus SoC, another group will receive tuberculosis treatment plus SoC, and another group will receive valganciclovir, tuberculosis treatment, and SoC.
- Conditions
- Pneumonia, HIV/AIDS, Tuberculosis, Cytomegalovirus Infections
- Being tested
- Valganciclovir Oral Solution [Valcyte], Tuberculostatic Agents
- Medical subject headings
- Pneumonia, Acquired Immunodeficiency Syndrome, Tuberculosis, Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valganciclovir Oral Solution [Valcyte]Drug
Also called Treatment for CMV
Treatment for CMV
Tuberculostatic AgentsDrug
Also called Treatment for TB
Treatment for tuberculosis
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care (SoC) | No intervention | Standard treatment for severe pneumonia and pneumonia in HIV-infected infants: Ceftriaxone 80 mg/k/day or Ampicillin plus Gentamicin ampicillin 50 mg/kg, or benzylpenicillin 50,000 unit/kg im/iv every six hours plus Gentamicin 7.5 mg/kg/im or iv once a day Cotrimoxazole trimethoprim (TMP) 8mg/kg/dose + sulfamethoxazole (SMX) 40mg/kg/dose three times daily Prednisolone 2mg/kg during 7 days, plus 1mg/kg other 7 days, plus 0.5 mg/kg for 7 days |
| Valganciclovir plus SoC | Experimental | Treatment for cytomegalovirus (CMV) Valganciclovir (powder for suspension, 50 mg/mL) oral, 16 mg/kg/12 hours for 15 days, and Standard or Care as described in Control Group Receives: Drug: Valganciclovir Oral Solution [Valcyte] |
| Tuberculosis Treatment plus SoC | Experimental | Treatment for tuberculosis Fixed-dose dispersible tablet of rifampicin, isoniazid, pyrazinamide (75/50/150 mg) Fixed-dose dispersible tablet of rifampicin/isoniazid (75/50 mg) Ethambutol 100 mg dispersible tablet Plus Standard of Care described in the Control Group
Doses of tuberculosis treatment:
Isoniazid 10 mg/kg (range 7-15 mg/kg)/day; maximum dose 300 mg/day for 6 months.
Rifampicin 15 mg/kg (range 10-20 mg/kg)/day; maximum dose 600 mg/day for 6 months.
Pyrazinamide 35 mg/kg (range 30-40 mg/kg)/day for 2 months. Ethambutol 20 mg/kg (range 15-25 mg/kg)/day for 2 months. Receives: Drug: Tuberculostatic Agents |
| Tuberculosis Treatment plus Valganciclovir plus SoC | Experimental | Treatment for CMV and for tuberculosis. Fixed-dose dispersible tablet of rifampicin, isoniazid, pyrazinamide (75/50/150 mg) Fixed-dose dispersible tablet of rifampicin/isoniazid (75/50 mg) Ethambutol 100 mg dispersible tablet Valganciclovir (powder for suspension, 50 mg/mL) oral, 16 mg/kg/12 hours for 15 days, Plus Standard of Care described in the Control Group
Doses of tuberculosis treatment:
Isoniazid 10 mg/kg (range 7-15 mg/kg)/day; maximum dose 300 mg/day for 6 months.
Rifampicin 15 mg/kg (range 10-20 mg/kg)/day; maximum dose 600 mg/day for 6 months.
Pyrazinamide 35 mg/kg (range 30-40 mg/kg)/day for 2 months. Ethambutol 20 mg/kg (range 15-25 mg/kg)/day for 2 months. Receives: Drug: Valganciclovir Oral Solution [Valcyte]; Drug: Tuberculostatic Agents |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
The primary endpoint of the study is all-cause mortality, focusing on the short term (up to 15-days) and long-term (up to 1-year) mortality. Mortality will be calculated using all-cause mortality after the admission over all the trial time.
Measured: 1 year
Secondary outcomes (15)
Days with oxygen therapy
- Duration of oxygen requirements (in days, from the first requirement until definitive withdrawal, being day 1 the first day of oxygen requirement).
Measured: 60 days
Days of hospitalization
- Cumulative days of hospitalization from discharge to day +365 after enrollment
Measured: 1 year
Serious Adverse Events
Serious Adverse Events (SAEs), this is, grade 3 and 4 AEs.
Measured: 1 year
Adverse Reactions
Adverse Reactions (AR)
Measured: 1 year
Notable Adverse Events
Adverse events (AEs) requiring stop of investigational medical product (IMP), all AEs relevant for risk/benefit ratio, including infections, liver toxicity, neurological and optic toxicity, renal, hematological and any AE grade 1, 2, 3 or 4 that the investigator estimates to be relevant
Measured: 1 year
Immune-reconstitution inflammatory syndrome
Incidence of TB-related immune-reconstitution inflammatory syndrome (IRIS)
Measured: 6 months
Baseline cytomegalovirus prevalence
Baseline prevalence of CMV infection and CMV-attributable pneumonia (based in a CMV viral load threshold) in recruited HIV-infected infants with severe pneumonia
Measured: 30 days
Baseline tuberculosis prevalence
Baseline prevalence of microbiological confirmed and unconfirmed TB (according to Graham criteria, Updated Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children 2015) in recruited HIV-infected patients with severe pneumonia
Measured: 60 days
Tuberculosis incidence
New confirmed and unconfirmed TB cases according to Graham criteria during 1-year of follow-up among patients without TB-T
Measured: 1 year
Deaths attributable to tuberculosis
Proportion of confirmed and unconfirmed TB, according to Graham criteria, in died children
Measured: 1 year
CMV prevalence in died participants
Proportion of CMV infection in died children
Measured: 1 year
CMV Molecular response to treatment
Reduction of quantitative CMV viral load in blood and saliva in infants treated with valganciclovir from enrollment to day +15
Measured: 1 year
TB-lipoarabinomannan (LAM) sensitivity and specificity
To assess the diagnostic accuracy (sensitivity and specificity) of TB-LAM for the diagnosis of confirmed TB (reference: positive Xpert Mycobacterium tuberculosis (MTB)/RIF Ultra in feces and/or NPA)
Measured: 1 year
Quality-adjusted life expectancy
Economic evaluation for quality-adjusted life expectancy
Measured: 1 year
Per-patient cost
Economic evaluation of the treatments (per-patient cost)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2019
- Study start1 Mar 2020
- Primary completion31 Jan 2025
- Study completion31 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 563 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario 12 de Octubre
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Bordeaux, Institut National de la Santé Et de la Recherche Médicale, France, PENTA Foundation, Centre Hospitalier Cocody, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Eduardo Mondlane University, Centro de Investigação em Saúde de Manhiça, Stichting Katholieke Universiteit, Barcelona Institute for Global Health, University of Lincoln, Makerere University, University Teaching Hospital, Lusaka, Zambia, University of Zimbabwe, Kamuzu Central Hospital, Servicio Madrileño de Salud, Madrid, Spain
- Responsible party
- Sponsor
- Investigators
- Cinta Moraleda, MD, PhD, Study chair, Hospital Universitario 12 de Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03915366
- Sponsor's protocol ID
- 19/096
- Other IDs
- 2019-001749-42, EDCTP RIA2017MC-2013EMPIRICAL, U1111-1231-4736, PACTR201904797961340, 2019
- Acronym
- EMPIRICAL
- Status last verified
- Sep 2025
- First submitted
- 10 Apr 2019
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After principal results, addressing primary and secondary objectives will be published. A final repository will be chosen for anonymized data sharing, and transparency after the trial is closed, according to the funder (EDCTP) rules and recommendations, unless national laws impede it.
Publications
Moraleda C, Tagarro A, Dominguez-Rodriguez S, Musiime V, Mujuru H, Chabala C, Mvalo T, Iroh-Tam PY, Bramugy J, Madrid L, Sacarlal J, Passanduca A, Sidat M, Cassia U, Aanyu HT, Tagoola A, Mutata C, Nduna B, Chawinga C, Ghambi L, Bates M, Fernandez-Luis S, Seni A, Gafur M, Nalwanga D, Nansera D, Bwakura-Dangarembizi M, Namuziya N, Egbe FN, Tembo J, Ballesteros A, Moh R, Manukyan L, Lora D, Marcy O, Jacobs TG, Burger D, Bassat Q, Leroy V, Nardone A, Buck WC, Rojo P; Empirical Clinical Trial Group. Empirical treatment with valganciclovir in infants living with HIV and hospitalised with severe pneumonia in Africa: a multicentre, open-label, factorial, randomised, controlled, superiority trial. Lancet. 2026 Jul 17:S0140-6736(26)00754-3. doi: 10.1016/S0140-6736(26)00754-3. Online ahead of print.
PubMed 42468541Jacobs TG, Mumbiro V, Tembo J, Egbe FN, Moraleda C, Beca LSDAB, Passanduca A, Kakooza L, Chitsamatanga M, Nduna B, Bramugy J, Tagarro A, Chhaganlal KD, Mutesi S, Mark NL, Bwakura-Dangarembizi M, Namuzizya N, Ballesteros A, Dominguez-Rodriguez S, Colbers A, Sacarlal J, Nalwanga D, Mujuru HA, Chabala C, Madrid L, Buck WC, Musiime V, Bates M, Rojo P, Burger DM; EMPIRICAL Clinical Trial Group. Pharmacokinetics and pharmacodynamics of valganciclovir in infants with severe HIV-associated pneumonia in Africa: a sub-study of the EMPIRICAL randomised controlled trial. EClinicalMedicine. 2026 Apr 13;94:103899. doi: 10.1016/j.eclinm.2026.103899. eCollection 2026 Apr.
PubMed 42016921Dominguez-Rodriguez S, Lora D, Tagarro A, Moraleda C, Ballesteros A, Madrid L, Manukyan L, Marcy O, Leroy V, Nardone A, Burger D, Bassat Q, Bates M, Moh R, Tam PI, Mvalo T, Magallhaes J, Buck WC, Sacarlal J, Mussime V, Chabala C, Mujuru HA, Rojo P; EMPIRICAL group. Statistical analysis plan for the "empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia" clinical trial. Trials. 2025 Apr 30;26(1):144. doi: 10.1186/s13063-025-08841-7.
PubMed 40307889Jacobs TG, Mumbiro V, Chitsamatanga M, Namuziya N, Passanduca A, Dominguez-Rodriguez S, Tagarro A, Nathoo KJ, Nduna B, Ballesteros A, Madrid L, Mujuru HA, Chabala C, Buck WC, Rojo P, Burger DM, Moraleda C, Colbers A; EMPIRICAL Clinical Trial Group; EMPIRICAL Clinical Trial Group. Brief Report: Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change. J Acquir Immune Defic Syndr. 2023 May 1;93(1):42-46. doi: 10.1097/QAI.0000000000003168. Epub 2023 Apr 1.
PubMed 36724434Rojo P, Moraleda C, Tagarro A, Dominguez-Rodriguez S, Castillo LM, Tato LMP, Lopez AS, Manukyan L, Marcy O, Leroy V, Nardone A, Burger D, Bassat Q, Bates M, Moh R, Iroh Tam PY, Mvalo T, Magallhaes J, Buck WC, Sacarlal J, Musiime V, Chabala C, Mujuru HA. Empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia: study protocol for a multicenter, open-label randomized controlled clinical trial. Trials. 2022 Jun 27;23(1):531. doi: 10.1186/s13063-022-06203-1.
PubMed 35761406
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Empirical Treatment Against Cytomegalovirus and Tuberculosis in HIV-infected Infants With Severe Pneumonia: a Multicenter, Open-label Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT03915366
- Acronym / sponsor ID
- EMPIRICAL / 19/096
- Conditions
- Pneumonia, HIV/AIDS, Tuberculosis, Cytomegalovirus Infections
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 563 participants (actual)
- Lead sponsor
- Hospital Universitario 12 de OctubreUniversity, hospital or other
- Collaborators
- University Hospital, Bordeaux, Institut National de la Santé Et de la Recherche Médicale, France, PENTA Foundation, Centre Hospitalier Cocody, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Eduardo Mondlane University, Centro de Investigação em Saúde de Manhiça, Stichting Katholieke Universiteit, Barcelona Institute for Global Health, University of Lincoln, Makerere University, University Teaching Hospital, Lusaka, Zambia, University of Zimbabwe, Kamuzu Central Hospital, Servicio Madrileño de Salud, Madrid, Spain
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 31 Jan 2025 (actual)
- Study completion
- 31 Jan 2025 (actual)
- First posted
- 16 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will evaluate whether empirical treatment against cytomegalovirus and tuberculosis improves survival of HIV-infected infants with severe pneumonia.
Detailed description
Pneumonia is the main cause of death in Human Immunodeficiency Virus (HIV)-infected children. A significant number of undiagnosed or poorly treated HIV-infected children present to health services with severe pneumonia. World Health Organization (WHO) guidelines to treat severe pneumonia in HIV-infected infants include empirical treatment against common bacteria plus Pneumocystis jirovecii. Although this approach has contributed to reducing overall case fatality rates, mortality in this particularly vulnerable group remains unacceptably high. Autopsy studies in Africa have shown that cytomegalovirus (CMV) infection and tuberculosis (TB) are important underdiagnosed and undertreated causes of deaths. Our objective is to evaluate whether empirical treatment against cytomegalovirus and tuberculosis improves survival of HIV-infected infants with severe pneumonia. A randomized factorial clinical trial will be conducted in six sub-Saharan African countries to evaluate the safety and efficacy of empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants aged 28 days to 365 days admitted to hospital with severe pneumonia. The primary outcome is mortality. All HIV-infected infants will receive standard of care (SoC) pneumonia treatment, including antibiotics, cotrimoxazole, and prednisolone. A group of patients will receive SoC, another group will receive valganciclovir plus SoC, another group will receive tuberculosis treatment plus SoC, and another group will receive valganciclovir, tuberculosis treatment, and SoC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Standard of Care (SoC) | No intervention | –Standard treatment for severe pneumonia and pneumonia in HIV-infected infants: Ceftriaxone 80 mg/k/day or Ampicillin plus Gentamicin ampicillin 50 mg/kg, or benzylpenicillin 50,000 unit/kg im/iv every six hours plus Gentamicin 7.5 mg/kg/im or iv once a day Cotrimoxazole trimethoprim (TMP) 8mg/kg/dose + sulfamethoxazole (SMX) 40mg/kg/dose three times daily Prednisolone 2mg/kg during 7 days, plus 1mg/kg other 7 days, plus 0.5 mg/kg for 7 days |
| Valganciclovir plus SoC | Experimental | Drug: Valganciclovir Oral Solution [Valcyte]Treatment for cytomegalovirus (CMV) Valganciclovir (powder for suspension, 50 mg/mL) oral, 16 mg/kg/12 hours for 15 days, and Standard or Care as described in Control Group |
| Tuberculosis Treatment plus SoC | Experimental | Drug: Tuberculostatic AgentsTreatment for tuberculosis Fixed-dose dispersible tablet of rifampicin, isoniazid, pyrazinamide (75/50/150 mg) Fixed-dose dispersible tablet of rifampicin/isoniazid (75/50 mg) Ethambutol 100 mg dispersible tablet Plus Standard of Care described in the Control Group Doses of tuberculosis treatment: Isoniazid 10 mg/kg (range 7-15 mg/kg)/day; maximum dose 300 mg/day for 6 months. Rifampicin 15 mg/kg (range 10-20 mg/kg)/day; maximum dose 600 mg/day for 6 months. Pyrazinamide 35 mg/kg (range 30-40 mg/kg)/day for 2 months. Ethambutol 20 mg/kg (range 15-25 mg/kg)/day for 2 months. |
| Tuberculosis Treatment plus Valganciclovir plus SoC | Experimental | Drug: Valganciclovir Oral Solution [Valcyte], Drug: Tuberculostatic AgentsTreatment for CMV and for tuberculosis. Fixed-dose dispersible tablet of rifampicin, isoniazid, pyrazinamide (75/50/150 mg) Fixed-dose dispersible tablet of rifampicin/isoniazid (75/50 mg) Ethambutol 100 mg dispersible tablet Valganciclovir (powder for suspension, 50 mg/mL) oral, 16 mg/kg/12 hours for 15 days, Plus Standard of Care described in the Control Group Doses of tuberculosis treatment: Isoniazid 10 mg/kg (range 7-15 mg/kg)/day; maximum dose 300 mg/day for 6 months. Rifampicin 15 mg/kg (range 10-20 mg/kg)/day; maximum dose 600 mg/day for 6 months. Pyrazinamide 35 mg/kg (range 30-40 mg/kg)/day for 2 months. Ethambutol 20 mg/kg (range 15-25 mg/kg)/day for 2 months. |
Who may qualify
- Ages
- 28 to 365 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (17 listed)
- Age 28 days to 365 days of age
- Pneumonia defined as chest indrawing or fast breathing for age, for infants 28 to 60 days of age ≥60 breaths per minute and for infants 61 to 365 days of age, ≥50 breaths per minute.
- Current hospitalization due to pneumonia with criteria for parenteral antibiotics (1 or more criteria)
- HIV-confirmed infection (with at least one molecular method: DNA polymerase chain reaction (PCR) or RNA PCR/viral load).
- Informed consent obtained
Key exclusion criteria (11 listed)
- Clinical TB (pulmonary or extrapulmonary) diagnosis, defined as the necessity of TB-T prescribed by a physician, at the moment of randomization
- Known bacteriologically confirmed TB case (at least one biological specimen positive by culture or Xpert MTB/RIF) at the moment of randomization
- Patient previously treated for TB or currently on treatment for TB
- Documented evidence of close TB exposure (household contact of a patient with documented TB during the lifetime of the child, or currently receiving TB-T)
- Pure wheezers defined as a clear clinical improvement after a bronchodilator test (give a challenge of rapid-acting inhaled bronchodilator for up to three times 15-20 minutes apart. Count the breaths and look for chest indrawing again, and then re-classify)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valganciclovir Oral Solution [Valcyte]Also: Treatment for CMVTreatment for CMV | Drug | Tuberculosis Treatment plus Valganciclovir plus SoC, Valganciclovir plus SoC |
| Tuberculostatic AgentsAlso: Treatment for TBTreatment for tuberculosis | Drug | Tuberculosis Treatment plus SoC, Tuberculosis Treatment plus Valganciclovir plus SoC |
Primary outcome
Mortality
Time frame: 1 year
The primary endpoint of the study is all-cause mortality, focusing on the short term (up to 15-days) and long-term (up to 1-year) mortality. Mortality will be calculated using all-cause mortality after the admission over all the trial time.
15 secondary outcomes
Days with oxygen therapy
Time frame: 60 days
Days of hospitalization
Time frame: 1 year
Serious Adverse Events
Time frame: 1 year
Adverse Reactions
Time frame: 1 year
Notable Adverse Events
Time frame: 1 year
Immune-reconstitution inflammatory syndrome
Time frame: 6 months
Baseline cytomegalovirus prevalence
Time frame: 30 days
Baseline tuberculosis prevalence
Time frame: 60 days
Tuberculosis incidence
Time frame: 1 year
Deaths attributable to tuberculosis
Time frame: 1 year
CMV prevalence in died participants
Time frame: 1 year
CMV Molecular response to treatment
Time frame: 1 year
TB-lipoarabinomannan (LAM) sensitivity and specificity
Time frame: 1 year
Quality-adjusted life expectancy
Time frame: 1 year
Per-patient cost
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Derived from this study: PubMed 42468541Moraleda C, Tagarro A, Dominguez-Rodriguez S, Musiime V, Mujuru H, Chabala C, Mvalo T, Iroh-Tam PY, Bramugy J, Madrid L, Sacarlal J, Passanduca A, Sidat M, Cassia U, Aanyu HT, Tagoola A, Mutata C, Nduna B, Chawinga C, Ghambi L, Bates M, Fernandez-Luis S, Seni A, Gafur M, Nalwanga D, Nansera D, Bwakura-Dangarembizi M, Namuziya N, Egbe FN, Tembo J, Ballesteros A, Moh R, Manukyan L, Lora D, Marcy O, Jacobs TG, Burger D, Bassat Q, Leroy V, Nardone A, Buck WC, Rojo P; Empirical Clinical Trial Group. Empirical treatment with valganciclovir in infants living with HIV and hospitalised with severe pneumonia in Africa: a multicentre, open-label, factorial, randomised, controlled, superiority trial. Lancet. 2026 Jul 17:S0140-6736(26)00754-3. doi: 10.1016/S0140-6736(26)00754-3. Online ahead of print.
- Derived from this study: PubMed 42016921Jacobs TG, Mumbiro V, Tembo J, Egbe FN, Moraleda C, Beca LSDAB, Passanduca A, Kakooza L, Chitsamatanga M, Nduna B, Bramugy J, Tagarro A, Chhaganlal KD, Mutesi S, Mark NL, Bwakura-Dangarembizi M, Namuzizya N, Ballesteros A, Dominguez-Rodriguez S, Colbers A, Sacarlal J, Nalwanga D, Mujuru HA, Chabala C, Madrid L, Buck WC, Musiime V, Bates M, Rojo P, Burger DM; EMPIRICAL Clinical Trial Group. Pharmacokinetics and pharmacodynamics of valganciclovir in infants with severe HIV-associated pneumonia in Africa: a sub-study of the EMPIRICAL randomised controlled trial. EClinicalMedicine. 2026 Apr 13;94:103899. doi: 10.1016/j.eclinm.2026.103899. eCollection 2026 Apr.
- Derived from this study: PubMed 40307889Dominguez-Rodriguez S, Lora D, Tagarro A, Moraleda C, Ballesteros A, Madrid L, Manukyan L, Marcy O, Leroy V, Nardone A, Burger D, Bassat Q, Bates M, Moh R, Tam PI, Mvalo T, Magallhaes J, Buck WC, Sacarlal J, Mussime V, Chabala C, Mujuru HA, Rojo P; EMPIRICAL group. Statistical analysis plan for the "empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia" clinical trial. Trials. 2025 Apr 30;26(1):144. doi: 10.1186/s13063-025-08841-7.
- Derived from this study: PubMed 36724434Jacobs TG, Mumbiro V, Chitsamatanga M, Namuziya N, Passanduca A, Dominguez-Rodriguez S, Tagarro A, Nathoo KJ, Nduna B, Ballesteros A, Madrid L, Mujuru HA, Chabala C, Buck WC, Rojo P, Burger DM, Moraleda C, Colbers A; EMPIRICAL Clinical Trial Group; EMPIRICAL Clinical Trial Group. Brief Report: Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change. J Acquir Immune Defic Syndr. 2023 May 1;93(1):42-46. doi: 10.1097/QAI.0000000000003168. Epub 2023 Apr 1.
- Derived from this study: PubMed 35761406Rojo P, Moraleda C, Tagarro A, Dominguez-Rodriguez S, Castillo LM, Tato LMP, Lopez AS, Manukyan L, Marcy O, Leroy V, Nardone A, Burger D, Bassat Q, Bates M, Moh R, Iroh Tam PY, Mvalo T, Magallhaes J, Buck WC, Sacarlal J, Musiime V, Chabala C, Mujuru HA. Empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia: study protocol for a multicenter, open-label randomized controlled clinical trial. Trials. 2022 Jun 27;23(1):531. doi: 10.1186/s13063-022-06203-1.
- Individual participant dataSharing planned: Yes. After principal results, addressing primary and secondary objectives will be published. A final repository will be chosen for anonymized data sharing, and transparency after the trial is closed, according to the funder (EDCTP) rules and recommendations, unless national laws impede it.
Related trials for Pneumonia
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Not yet recruiting
Expanded Diagnostic Strategy in Older Adults Hospitalized With Community-Acquired Acute Respiratory Infection
Acute Respiratory Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cinta Moraleda, MD, PhD study chair
Hospital Universitario 12 de Octubre
13 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Valganciclovir Oral Solution [Valcyte] and Tuberculostatic Agents in people with Pneumonia and HIV/AIDS, run by Hospital Universitario 12 de Octubre at 13 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in France, Mozambique, Côte d’Ivoire, Italy, Malawi and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03915366, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.