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Daily adjunctive therapy with vitamin D 3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia
Author(s) -
Bekele A.,
Gebreselassie N.,
Ashenafi S.,
Kassa E.,
Aseffa G.,
Amogne W.,
Getachew M.,
Aseffa A.,
Worku A.,
Raqib R.,
Agerberth B.,
Hammar U.,
Bergman P.,
Aderaye G.,
Andersson J.,
Brighenti S.
Publication year - 2018
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12767
Subject(s) - medicine , placebo , sputum , gastroenterology , adverse effect , tuberculosis , randomized controlled trial , intention to treat analysis , clinical trial , clinical endpoint , vitamin , surgery , pathology , alternative medicine
Objective Immunotherapy using vitamin D (vitD 3 ) and phenylbutyrate ( PBA ) may support standard drug regimens used to treat infectious diseases. We investigated if vitD 3 + 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 vitD 3 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 (m ITT , 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 )D 3 concentrations. Results Most subjects had low baseline plasma 25( OH )D 3 levels that increased gradually in the vitD 3 + 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 m ITT 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). VitD 3 + 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 vitD 3 + PBA group (12.6%). Conclusion Daily supplementation with vitD 3 + PBA may ameliorate clinical TB symptoms and disease‐specific complications, while the intervention had no effect on bacterial clearance in sputum.