Empirical Treatment Against Cytomegalovirus and Tuberculosis in HIV-infected Infants With Severe Pneumonia (EMPIRICAL)
Pneumonia, HIV/AIDS, Tuberculosis
About this trial
This is an interventional treatment trial for Pneumonia
Eligibility Criteria
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
Sites / Locations
- Programme PACCI. Centre Hospitalier Cocody.Recruiting
- Université de Bourdeaux
- INSERM
- PENTA Foundation
- Malawi Liverpool Welcome Trust. Queen Elizabeth Central Hospital College of MedicineRecruiting
- Cemtro de Investigaçao em Saúde da ManhiçaRecruiting
- Hospital Central MaputoRecruiting
- Stichting Katholieke Universiteit Radboudumc
- Fundación para la Investigación Biomédica del Hospital 12 de Octubre
- Makerere University - Mulago HospitalRecruiting
- University of Lincoln
- Lusaka Teaching HospitalRecruiting
- University of Zimbabwe Clinical Research CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
No Intervention
Experimental
Experimental
Experimental
Standard of Care (SoC)
Valganciclovir plus SoC
Tuberculosis Treatment plus SoC
Tuberculosis Treatment plus Valganciclovir plus SoC
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
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
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.
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.