Table 2.
Human clinical trial data for host-directed therapy for TBa
| Drug (reference[s]) | Sample size, n (population) | Intervention | Key results and comments |
|---|---|---|---|
| Aspirin (83, 94) | 119 (TBM) | RCT, aspirin 150 mg p.o. daily vs placebo; all received standard TB treatment; some received prednisolone | Stroke risk, aspirin vs placebo, OR 0.42 (95% CI 0.12–1.39, P = 0.18); death risk, placebo vs aspirin, OR 2.76 (95% CI 1.05–7.39, P = 0.03); prednisolone use was not standardized and was used more frequently in survivors and those who did not develop a new stroke |
| Aspirin (93) | 159 (TBM) | RCT, placebo vs aspirin 75 mg daily vs aspirin 100 mg/kg daily; all received standard TB treatment with prednisolone | No difference in mortality or morbidity among groups |
| Etanercept (141, 142) | 16 (PTB) | Single-arm trial of etanercept (n = 16) started on day 4 of TB treatment compared to historical controls (n = 42) | SCC slightly more rapid in etanercept group (median, 56 vs 63 days; P = 0.05) |
| IFN-γ (138) | 96 (PTB) | RCT, IFN-γ nebulized vs IFN-γ subcutaneous vs placebo; all received standard TB treatment | Higher SSC at 4 wk in IFN-γ group (P = 0.03); trend to higher SCC at 4 wk in IFN-γ group (P = 0.15); disease symptoms were less in both IFN-γ treatment groups |
| IFN-γ (137) | 32 (nontuberculous mycobacterial lung disease) | RCT, IFN-γ intramuscularly vs placebo; all received standard NTM treatment | IFN-γ group with improvement of symptoms compared to controls (6-mo complete responders, 72% vs 36%; P = 0.037); higher SCC at 18 mo in IFN-γ group (P = 0.04); radiographic improvement higher in IFN-γ group at 18 mo (P = 0.036) |
| IFN-γ (202) | 5 (PTB, MDR) | Open-label aerosol IFN-γ | Aerosolized IFN-γ was well tolerated by 5 MDR TB patients; treated patients showed steady wt gain; 4/5 treated patients switched from sputum smear positive to negative after 4 wk of treatment; chest CT scans showed improvement in all 5 treated patients |
| Pentoxifylline (152) | 120 (PTB) | RCT, pentoxifylline vs placebo; all received standard TB treatment | No difference in M. tuberculosis culture conversion, radiographic improvement, or death |
| Thalidomide (147) | 47 (TBM) | RCT, thalidomide vs placebo; all received standard TB treatment including prednisolone | Study stopped early because all adverse events (rash, hepatitis, death) occurred in thalidomide group |
| Vitamin D2 (200) | 192 (contacts of TB cases, United Kingdom) | RCT, placebo vs vitamin D2 (single dose of 2.5 mg) | Primary outcome, BCG growth in whole-blood assay; 24-h growth down in vitamin D group; no difference at 96 h |
| Vitamin D (53) | 67 (PTB, Indonesia) | RCT, placebo vs vitamin D (type not defined) (25 mg/day over 6 wk); all received standard TB treatment | Primary outcome, not specified; longer SSC in vitamin D group than in placebo group at 6 wk (77 vs 100%, P = 0.002) |
| Vitamin D3 (55, 56) | 146 (PTB, United Kingdom) | RCT, placebo vs vitamin D3 (2.5 mg × 4 doses over 42 days); all received standard TB treatment | Primary outcome, SCC; trend toward shorter SCC in vitamin D group but not significant; VDR TaqI tt genotype significantly lower time to conversion (but not Tt or TT genotype) |
| Vitamin D3 (57) | 365 (PTB, Guinea-Bissau) | RCT, placebo vs vitamin D3 (100,000 IU × 3 over 8 mo); all received standard TB treatment | Primary outcome, clinical improvement as assessed by clinical severity TB score; no difference in TB score, SSC, wt gain, or all-cause mortality |
| Vitamin D3 (54) | 30 (PTB, India, all with diabetes) | RCT, placebo vs vitamin D3 (60,000 IU p.o. per wk for 6 wk) + calcium carbonate (1,000 mg/day); all received standard TB treatment | Primary outcome, SSC; trend toward shorter SSC in vitamin D group (8 wk vs 6 wk; P = 0.067) |
a
Abbreviations: MDR, multidrug resistant; OR, odds ratio; CI, confidence interval; p.o., orally; PTB, pulmonary tuberculosis; RCT, randomized controlled trial; SCC, sputum culture conversion; SSC, sputum smear conversion; TBM, TB meningitis; NTM, nontuberculous mycobacteria; CT, computed tomography.