Journal Article

Levofloxacin versus placebo for the prevention of tuberculosis disease in child contacts of multidrug-resistant tuberculosis: study protocol for a phase III cluster randomised controlled trial (TB-CHAMP)

Fairlie, Lee, Martinson, Neil, Garcia-Prats, Anthony J., Hoddinott, Graeme, Crook, Angela M., Owen-Powell, Ellen, Schaaf, H. Simon, Thomason, Margaret J., Gibb, Diana M., Seddon, James A., Osman, Muhammad, Demers, Anne-Marie, Turkova, Anna, Hesseling, Anneke C., Purchase, Susan E.

2018

Overview

Background Multidrug-resistant (MDR) tuberculosis (TB) presents a challenge for global TB control. Treating individuals with MDR-TB infection to prevent progression to disease could be an effective public health strategy. Young children are at high risk of developing TB disease following infection and are commonly infected by an adult in their household. Identifying young children with household exposure to MDR-TB and providing them with MDR-TB preventive therapy could reduce the risk of disease progression. To date, no trials of MDR-TB preventive therapy have been completed and World Health Organization guidelines suggest close observation with no active treatment. Methods The tuberculosis child multidrug-resistant preventive therapy (TB-CHAMP) trial is a phase III cluster randomised placebo-controlled trial to assess the efficacy of levofloxacin in young child contacts of MDR-TB cases. The trial is taking place at three sites in South Africa where adults with MDR-TB are identified. If a child aged < 5 years lives in their household, we assess the adult index case, screen all household members for TB disease and evaluate any child aged < 5 years for trial eligibility. Eligible children are randomised by household to receive daily levofloxacin (15–20 mg/kg) or matching placebo for six months. Children are closely monitored for disease development, drug tolerability and adverse events. The primary endpoint is incident TB disease or TB death by one year after recruitment. We will enrol 1556 children from approximately 778 households with an average of two eligible children per household. Recruitment will run for 18–24 months with all children followed for 18 months after treatment. Qualitative and health economic evaluations are embedded in the trial. Discussion If the TB-CHAMP trial demonstrates that levofloxacin is effective in preventing TB disease in young children who have been exposed to MDR-TB and that it is safe, well tolerated, acceptable and cost-effective, we would expect that that this intervention would rapidly transfer into policy. Trial registration ISRCTN Registry, ISRCTN92634082 . Registered on 31 March 2016.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adults / Age Factors / Analysis / Antibiotics / Antitubercular Agents - administration & dosage / Antitubercular Agents - adverse effects / Antitubercular Agents - economics / Bacterial infections / Biomedicine / Child health / Child, Preschool / Children & youth / Clinical trials / Clinical Trials, Phase III as Topic / Comparative analysis / Contact Tracing / Cost-Benefit Analysis / Disease prevention / Dosage and administration / Drug Administration Schedule / Drug Costs / Drug dosages / Drug resistance / Drug therapy / Female / Health Sciences / HIV / Housing / Human immunodeficiency virus / Humans / Infant / Infections / Levofloxacin / Levofloxacin - administration & dosage / Levofloxacin - adverse effects / Levofloxacin - economics / Male / Medicine / Medicine & Public Health / Multicenter Studies as Topic / Multidrug resistant organisms / Mutation / Pediatrics / Pharmacokinetics / Placebos / Prevention / Randomised / Randomized Controlled Trials as Topic / Resistant / South Africa / Statistics for Life Sciences / Study Protocol / Time Factors / Treatment Outcome / Trial / Tuberculosis / Tuberculosis, Multidrug-Resistant - economics / Tuberculosis, Multidrug-Resistant - microbiology / Tuberculosis, Multidrug-Resistant - prevention & control / Tuberculosis, Multidrug-Resistant - transmission