Empirical Treatment Against Cytomegalovirus and Tuberculosis in HIV-infected Infants With Severe Pneumonia

  • STATUS
    Recruiting
  • End date
    Jan 31, 2024
  • participants needed
    624
  • sponsor
    Hospital Universitario 12 de Octubre
Updated on 5 March 2021

Summary

This trial will evaluate whether empirical treatment against cytomegalovirus and tuberculosis improves survival of HIV-infected infants with severe pneumonia.

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.

Details
Condition Tuberculosis, Pulmonary Disease, Lung Disease, Cytomegalic Inclusion Disease, Cytomegalovirus (CMV) Retinitis, Cytomegalovirus Infections, Upper respiratory infection, Throat and Tonsil Infections, Pneumonia, Pneumonia, Pneumonia (Pediatric), Cytomegalovirus, Throat and Tonsil Infections, Cytomegalovirus (CMV) Retinitis, Pneumonia (Pediatric), HCMV Infection, Lung Disease, Cytomegalovirus Infections, cytomegalovirus infection, pneumoniae, pneumonitis, lung inflammation, tb (tuberculosis), cmv infection, HIV/AIDS, HIV/AIDS, HIV/AIDS
Treatment Valganciclovir Oral Solution [Valcyte], Tuberculostatic Agents, Tuberculostatic Agents
Clinical Study IdentifierNCT03915366
SponsorHospital Universitario 12 de Octubre
Last Modified on5 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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
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
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