A phase III cluster randomised placebo‐controlled trial to assess the efficacy of preventive therapy in child contacts of multidrug‐resistant (MDR) tuberculosis (TB)
This trial specifically targets children less than five years for two reasons. First, children less than five years are at the highest risk of progressing to TB disease following infection. Second, concordance of drug susceptibility is high between adults with MDR‐TB and young child household contacts. This group is therefore most likely to be benefit from MDR‐TB preventive therapy. In addition, global policy and national guidelines in South Africa advocate preventive therapy only for HIV‐negative child contacts less than five years following exposure to a drug‐susceptible TB index case, enhancing the programmatic relevance of our proposed trial. Furthermore, this trial targets children (HIV‐infected and uninfected) under 5 years of age, regardless of tuberculin skin test (TST) status, to ensure programmatic relevance, since WHO and the South African National TB Programme (SA NTP) do not mandate tests of TB infection prior to initiating TB preventive therapy.
To determine whether LFX, the intervention arm, given daily for 24 weeks, is efficacious in preventing MDR‐TB in high‐risk child household contacts (HHC) of confirmed adult MDR‐TB cases.
• Does LFX have acceptable toxicity and tolerability in children?
• Is mortality (non‐traumatic death) similar in children on the 2 study arms?
• What is the adherence to 24 weeks of daily MDR‐TB prevention?
• Are there differences in LFX resistance between study arms in children developing incident TB?
• Is LFX cost‐effective and acceptable to both families and to the TB programme in preventing MDR‐TB in child household contacts
This Study is made possibleint Global Health Trials Scheme of the Department for International Development, UK (DFID), the Wellcome Trust and the Medical Research Council (MRC UK), Grant number MR/M007340/1 and the South African Medical Research Council (SA MRC). Trial drugs will be supplied by McCleods, India. In partnership with Desmond Tutu TB Centre (DTTC) (Prof Anneke Hesseling)