HIV/AIDS Tuberculosis Cytomegalovirus pneumonia Respiratory Paediatrics
Conditions
Interventions
Standard of Care
TBT plus Standard of Care
Valganciclovir plus Standard of Care
TBT plus Valganciclovir plus SoC
Sponsors
Servicio Madrileno de Salud Fundacion para la Investigacion Biomedica Hospital Universitario 12 de Octubre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 28 days to 365 days of age 2. 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. 3. Current hospitalization due to pneumonia with criteria for parenteral antibiotics (1 or more criteria) a) Chest indrawing with HIV infection b) No improvement with oral treatment. c) One or more danger signs according to WHO - 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 4. HIV-confirmed infection (with at least one molecular method: DNA PCR or RNA PCR/viral load). 5. Informed consent obtained
Exclusion criteria
Exclusion criteria: 1. Clinical TB (pulmonary or extrapulmonary) diagnosis, defined as the necessity of TB-T prescribed by a physician, at the moment of randomization 2. Known bacteriologically confirmed TB case (at least one biological specimen positive by culture or Xpert MTB/RIF) at the moment of randomization 3. Patient previously treated for TB or currently on treatment for TB 4. 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) 5. 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) 6. Active malignancies 7. Systemic immunosuppressive medications. Steroids will be considered to be immunosuppressing only if >2 mg/kg of prednisone or equivalent during >15 days 8. 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 9. Less than 2.5 kg of weight 10. Hb 6 g/dL if the patient’s state allows it. In case a transfusion is administered, the patient can be enrolled 11. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mortality | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of oxygen requirements (in days, from the first requirement until definitive withdrawal, being day 1 the first day of oxygen requirement). ;Cumulative days of hospitalization from discharge to day +365 after enrollment ;Serious Adverse Events (SAEs), this is, grade 3 and 4 AEs, Adverse Reactions, Adverse Events requiring stop of IMP, IRIS.;Prevalence of CMV infection;Baseline prevalence of Tuberculosis;Incidence of Tuberculosis;Proportion of CMV and Tuberculosis in died children;Reduction of quantitative CMV viral load in blood and saliva in infants treated with valganciclovir from enrollment to day +15;To assess the diagnostic accuracy of TB-LAM for the diagnosis of confirmed TB (reference: positive Xpert MTB/RIF Ultra in feces and/or NPA).;Quality-adjusted life expectancy and per-patient cost | — |
Countries
Cote Divoire, Malawi, Mozambique, Uganda, Zambia, Zimbabwe
Contacts
Public ContactLilit Manukyan
Fundacion 12 de Octubre
Outcome results
None listed