A Bekele1, N Gebreselassie2,3, S Ashenafi2, E Kassa1, G Aseffa4, W Amogne1, M Getachew1, A Aseffa3, A Worku5, R Raqib6, B Agerberth7, U Hammar8, P Bergman7, G Aderaye1, J Andersson2,9, S Brighenti2. 1. Department of Internal Medicine, Faculty of Medicine, Black Lion University Hospital, Addis Ababa University, Addis Ababa, Ethiopia. 2. Center for Infectious Medicine (CIM), F59, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. 3. Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia. 4. Department of Radiology, Faculty of Medicine, Black Lion University Hospital, Addis Ababa University, Addis Ababa, Ethiopia. 5. Department of Public Health, Faculty of Medicine, Black Lion University Hospital, Addis Ababa University, Addis Ababa, Ethiopia. 6. Infectious Diseases Division (IDD), International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh. 7. Clinical Microbiology, Department of Laboratory Medicine (Labmed), Karolinska Institutet, Stockholm, Sweden. 8. Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden. 9. Division of Infectious Diseases, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Abstract
OBJECTIVE:Immunotherapy using vitamin D (vitD3 ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB). METHODS: A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear-positive or smear-negative TB received daily oral supplementation with 5000 IU vitD3 and 2 × 500 mg PBA or placebo for 16 weeks, together with 6-month chemotherapy. Primary end-point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intention-to-treat (mITT, n = 348) and per-protocol (n = 296) analyses. Secondary end-points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25(OH)D3 concentrations. RESULTS: Most subjects had low baseline plasma 25(OH)D3 levels that increased gradually in the vitD3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. 127.4 nmol L-1 ). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (-0.52, 95% CI -0.93, -0.10; P = 0.015) while the modified TB score was reduced at week 8 (-0.58, 95% CI -1.02, -0.14; P = 0.01) and 16 (-0.34, 95% CI -0.64, -0.03; P = 0.03). VitD3 + PBA had no effect on longitudinal sputum-smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD3 + PBA group (12.6%). CONCLUSION:Daily supplementation with vitD3 + PBA may ameliorate clinical TB symptoms and disease-specific complications, while the intervention had no effect on bacterial clearance in sputum.
RCT Entities:
OBJECTIVE: Immunotherapy using vitamin D (vitD3 ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB). METHODS: A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear-positive or smear-negative TB received daily oral supplementation with 5000 IU vitD3 and 2 × 500 mg PBA or placebo for 16 weeks, together with 6-month chemotherapy. Primary end-point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intention-to-treat (mITT, n = 348) and per-protocol (n = 296) analyses. Secondary end-points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25(OH)D3 concentrations. RESULTS: Most subjects had low baseline plasma 25(OH)D3 levels that increased gradually in the vitD3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. 127.4 nmol L-1 ). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (-0.52, 95% CI -0.93, -0.10; P = 0.015) while the modified TB score was reduced at week 8 (-0.58, 95% CI -1.02, -0.14; P = 0.01) and 16 (-0.34, 95% CI -0.64, -0.03; P = 0.03). VitD3 + PBA had no effect on longitudinal sputum-smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD3 + PBA group (12.6%). CONCLUSION: Daily supplementation with vitD3 + PBA may ameliorate clinical TB symptoms and disease-specific complications, while the intervention had no effect on bacterial clearance in sputum.
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