Addressing Undernutrition As a Comorbidity in Tuberculosis: Outcomes in a Programmatic Cohort Nested Within the RATIONS Trial in Jharkhand, India

RATIONS trial is a field-based cluster-randomized trial of nutritional support to household contacts of adults with microbiologically-confirmed pulmonary tuberculosis (PTB) in Jharkhand, India aimed at reducing their TB incidence. The patient cohort in this trial was provided nutritional support, to assess its impact on TB-mortality and other outcomes.Methods: We enrolled 2800 patients across 28 tuberculosis units and provided food rations (1200 kcal, 52 gm proteins daily) and micronutrients. We recorded body mass index (BMI), diabetes status, and performance status with Eastern Cooperative Oncology Group (ECOG) scale (0-4; normal to bed-ridden). We recorded clinical, nutritional outcomes at six months, and determined the predictors of TB-mortality with Poisson and Cox regression using adjusted rate-ratios (aRR) and adjusted Hazard ratios (aHR).Results: At enrolment, 82% patients were underweight (BMI<18·5 kg/m2), 17% had a BMI<14 kg/m2. Mean weight and BMI were 42·6kg, 16·4 kg/m2 in men; and 36·1kg & 16·2 kg/m2 in women. At six months the outcomes included treatment success (94%), TB-mortality (3·9%), loss to follow up (1.0%), and treatment failure (<1%). The median weight gain was 4·6kg, but 55% patients remained underweight. At two months, 54% gained 5% of baseline weight. Baseline weight (aRR: 0·95, 95%CI 0·90–0·99), BMI (aRR: 0·88, 95%CI 0·76–1·01), poor performance status (ECOG categories 3-4) (aRR: 5·33, 95%CI 2·90—9.79), diabetes (aRR: 3·30, 95%CI:1·65–6·72), hemoglobin (aRR: 0·85, 95CI 0·71–1.00) were predictors of TB-mortality. There was 61% reduced hazard of death (aHR:0·39, 95%CI 0·18–0·86) associated with five percent weight gain at two months.Interpretation: Nutritional support in this cohort with high prevalence of severe undernutrition was associated with substantially decreased TB-mortality, improved adherence, treatment success, and weight gain compared to other programmatic cohorts in India. Nutritional support needs to be an integral component of patient-centred care to improve treatment outcomes in such settings.Trial Registration Details: Reducing Activation of Tuberculosis Through Improvement Of Nutritional Status (RATIONS) trial is an open-label, parallel-arm cluster-RCT involving household contacts (HHCs) of adult patients with microbiologically confirmed pulmonary tuberculosis (PTB) in Jharkhand state in eastern India registered with the Clinical Trials Registry of India (CTRI; CTRI/2019/08/020490).Funding Information: This work was supported by grants from the India Tuberculosis Research Consortium, Indian Council of Medical Research, New Delhi, India vide grant no 5/8/5/57/TB consortium/Call India Project/2017/ECD-1.Declaration of Interests: We declare no competing interests.Ethics Approval Statement: Ethics clearance was obtained from the Institutional Ethics Committee of the ICMR-NIRT (IEC number: 2018020). Local oversight was provided by the ethics committee of Ekjut, a non-profit organization involved in field-based research. Field staff obtained a written informed consent.