Evaluating the clinical and cost-effectiveness of Sodium Bicarbonate administration for critically ill patients with Acute Kidney Injury (MOSAICC – Multicentre evaluation Of Sodium bicarbonate in Acute kidney Injury in Critical Care)

Research question: In critically ill adults with metabolic acidosis and acute kidney injury (AKI) [Population], is treatment with intravenous (IV) 8.4% sodium bicarbonate [Intervention] superior to no IV sodium bicarbonate [Comparator] in terms of all-cause mortality at 90 days (clinical effectiveness) and incremental costs, QALYs and net monetary benefit at 90 days (cost-effectiveness) [Outcome]? Background: Critically ill patients with metabolic acidosis and AKI have a poor prognosis, with hospital and 90-day mortality of 56% and 59%, respectively. In such patients, renal replacement therapy (RRT) is often given, which is invasive and expensive. However, directly addressing the metabolic acidosis with a buffer solution (most commonly sodium bicarbonate) with the aim of raising extracellular pH to restore cardiovascular function and oxygen delivery to tissues, may improve outcomes and negate the need for RRT. To date there have been no RCTs primarily assessing the effects of sodium bicarbonate in critically ill patients with metabolic acidosis and AKI being treated in a critical care unit. Aims and objectives: To evaluate the clinical and cost-effectiveness of intravenous (IV) sodium bicarbonate (8.4%) in critically ill adults with acidosis and AKI on: all-cause mortality at 90 days following randomisation (primary clinical effectiveness outcome); incremental costs, quality-adjusted life years (QALYs) and net monetary benefit at 90 days (primary cost-effectiveness outcome); mortality at ICU discharge, 28 days and one year; receipt and duration of respiratory, renal, and advanced cardiovascular organ support; duration of ICU and acute hospital stay; on-going requirement for RRT at 90 days and one year; health-related quality of life at 90 days and one year; resource use and costs at 90 days and one year; and estimated lifetime incremental cost-effectiveness. Methods: Pragmatic multicentre, open, data-enabled RCT with internal pilot phase and integrated economic evaluation. Setting: 60 NHS critical care units participating in the Case Mix Programme (CMP) national clinical audit. Population: Critically ill adults with acidosis (pH <7.25, PaCO2 of <6.0 and bicarbonate 7.30 [Starting dose of 50ml (over 30-60 minutes) with repeated doses depending on subsequent pH readings and clinical status up to a maximum of 500ml/24hrs during the entire critical care unit stay or until commencement of RRT] Comparator: No IV sodium bicarbonate. Sample size: 2250 patients will achieve 90% power to detect a clinically meaningful reduction in 90-day mortality of 7% (p<0.05), allowing for 6% withdrawal/refusal of deferred consent. Timelines for delivery: 01/03/2021 to 31/12/2025 (58 months) Anticipated impact and dissemination: The results will be disseminated actively and extensively. This will cover both progress during the trial period and the results at the end of the study. Outputs will include, but will not be limited to, international and national meeting and conference presentations of study progress and results; publication of study; and incorporation into clinical guidelines. These separate outputs will be targeted at relevant stakeholders in formats suitable for the target audience. This will ensure that the potential benefit of the MOSAICC trial and its impact are maximised.