Simplifying and optimising management of acute malnutrition in children aged 6 to 59 months: study protocol for a 3 arms community-based individually randomised controlled trial in decentralised Niger.

BACKGROUND: Simplified approaches of acute malnutrition (AM) treatment have been conducted over the past 5 years intending to unify processes and increase coverage among children aged 6 to 59 months without medical complication. The Optimsing treatment for Acute Malnutrition (OptiMA) and the Combined Protocol for Acute Malnutrition Study (ComPAS) are mid-upper arm circumference (MUAC)-based approaches treating children with MUAC < 125 mm or oedema with one sole product-ready-to-use therapeutic food-at a gradually tapered doses. This trial aims to compare the OptiMA and ComPAS strategies to the standard nutritional protocol of Niger assessed by a favourable outcome in the treatment of uncomplicated AM at 6 months post-randomisation and in terms of recovery rate after treatment of uncomplicated SAM (WHZ < - 3 or MUAC < 115mm or oedema) and among the most vulnerable children (MUAC < 115mm or oedema). METHODS: A non-inferiority individually randomised controlled clinical trial was conducted at the primary health centres level and in the community in the Zinder region in Niger in March 2021. Participants are children aged 6-59 months attending outpatient health centres with MUAC < 125mm or oedema without medical complications. All participants are followed for 6 months. Simplified strategies propose a gradual reduction of RUTF according to MUAC and weight in OptiMA and MUAC only in ComPAS. Favourable outcome is compositely defined at 6 months post-inclusion as being alive, not acutely malnourished by the definition applied at inclusion and without any additional episode of AM throughout the 6-month observation period. Recovery is defined throughout the 6 months post-randomisation by a minimum of 4-week duration of treatment, an axillary temperature < 37.5°C, an absence of bipedal oedema and a MUAC ≥ 125 mm for two consecutive weeks. The sample size calculation required 567 children per arm for the main objective, 295 and 384 children per arm for the secondary objectives among SAM and MUAC < 115 mm children, respectively. Per-protocol and intention-to-treat analyses will be conducted for each outcome. DISCUSSION: This trial is intending to generate much-needed evidence on various simplified and optimised AM treatment approaches and to participate in reaching a consensus on such nutrition protocols. TRIAL REGISTRATION: ClinicalTrials.gov NCT04698070 . Registered on January 6, 2021.

Simplifying and optimising management of acute malnutrition in children aged 6 to 59 months: study protocol for a community-based individually randomised controlled trial in Kasaï, Democratic Republic of Congo.

INTRODUCTION: Acute malnutrition (AM) is a continuum condition, arbitrarily divided into moderate and severe AM (SAM) categories, funded and managed in separate programmes under different protocols. Optimising acute MAlnutrition (OptiMA) treatment aims to simplify and optimise AM management by treating children with mid-upper arm circumference (MUAC) <125 mm or oedema with one product-ready-to-use therapeutic food-at a gradually tapered dose. Our main objective was to compare the OptiMA strategy with the standard nutritional protocol in children 6-59 months presenting with MUAC <125 mm or oedema without additional complications, as well as in children classified as uncomplicated SAM (ie, MUAC <115 mm or weight-for-height Z-score (WHZ) <-3 or with oedema). METHODS AND ANALYSIS: This study was a non-inferiority, individually randomised controlled clinical trial conducted at community level in the Democratic Republic of Congo. Children 6-59 months presenting with MUAC <125 mm or WHZ <-3 or with bipedal oedema and without medical complication were included after signed informed consent in outpatient health facilities. All participants were followed for 6 months. Success in both arms was defined at 6 months post inclusion as being alive, not acutely malnourished per the definition applied at inclusion and without an additional episode of AM throughout the 6-month observation period. Recovery among children with uncomplicated SAM was the main secondary outcome. For the primary objective, 890 participants were needed, and 480 children with SAM were needed for the main secondary objective. We will perform non-inferiority analyses in per-protocol and intention-to-treat basis for both outcomes. ETHICS AND DISSEMINATION: Ethics approvals were obtained from the National Health Ethics Committee of the Democratic Republic of Congo and from the Ethics Evaluation Committee of Inserm, the French National Institute for Health and Medical Research (Paris, France). We will submit results for publication to a peer-reviewed journal and disseminate findings in international and national conferences and meetings. TRIAL REGISTRATION NUMBER: NCT03751475. Registered 19 September 2018, https://clinicaltrials.gov/ct2/show/NCT03751475.

Efficacy and safety of varenicline for smoking cessation in people living with HIV in France (ANRS 144 Inter-ACTIV): a randomised controlled phase 3 clinical trial.

BACKGROUND: Tobacco smoking is common in people living with HIV, but high-quality evidence on interventions for smoking cessation is not available in this population. We aimed to assess the efficacy and safety of varenicline with counselling to aid smoking cessation in people living with HIV. METHODS: The ANRS 144 Inter-ACTIV randomised, parallel, double-blind, multicentre, placebo-controlled phase 3 trial was done at 30 clinical hospital sites in France. People living with HIV who had smoked at least ten cigarettes per day for 1 year or longer, were motivated to stop smoking, were not dependent on another psychoactive substance, and had no history of depression or suicide attempt were eligible. Using a computer-generated randomisation sequence, we allocated (1:1) the patients to receive either varenicline titrated to two 0·5 mg doses twice daily or placebo twice daily for 12 weeks, plus face-to-face counselling. Patients and investigators were masked to treatment group allocation. Patients who were not abstinent at week 24 were offered open-label varenicline for 12 additional weeks. The primary outcome was the proportion of smokers continuously abstinent from week 9 to week 48. Smoking status was confirmed by carbon monoxide in exhaled air. Primary analyses were done in both the intention-to-treat (ITT) population and modified ITT (mITT) population, which comprised all patients who took at least one tablet of their assigned study treatment. The safety analyses were done in the mITT population. The trial is registered at ClinicalTrials.gov, number NCT00918307. The trial status is complete. FINDINGS: From Oct 26, 2009, to Dec 20, 2012, of 303 patients assessed for eligibility, 248 patients were randomly assigned to the varenicline group (n=123) or the placebo group (n=125). After randomisation, one participant initially assigned to the placebo group was excluded from the ITT analysis for a regulatory reason (no French health-care coverage). 102 patients in the varenicline group and 111 patients in the placebo group received at least one dose of their assigned treatment and were included in the mITT analysis. In the ITT analysis, varenicline was associated with a higher proportion of patients achieving continuous abstinence over the study period (week 9-48): 18 (15%, 95% CI 8-21) of 123 in the varenicline group versus eight (6%, 2-11) of 124 in the placebo group, adjusted odds ratio (OR) 2·5 (95% CI 1·0-6·1; p=0·041). In the mITT analysis, varenicline was also associated with higher continuous abstinence: 18 (18%, 95% CI 10-25) of 102 versus eight (7%, 2-12) of 111 in the placebo group (adjusted OR 2·7, 95% CI 1·1-6·5; p=0·029). The incidence of depression was 2·4 per 100 person-years (95% CI 0·6-9·5; two [2%] of 102) in the varenicline group and 12·4 per 100 person-years (95% CI 6·9-22·5; 11 [10%] of 111) in the placebo group. 14 (7%) of 213 participants had 18 cardiovascular events: six (6%) of 102 people in the varenicline group and eight (7%) of 111 people in the placebo group. INTERPRETATION: Varenicline is safe and efficacious for smoking cessation in people living with HIV and should be recommended as the standard of care. FUNDING: The French National Institute for Health and Medical Research (INSERM)-French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Pfizer.