Title: 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)
Funder: Department of Health and Social Care

Abstract: Around 184,000 critically ill adults are admitted to critical care units each year in the UK. Around half have a sudden worsening in kidney function that happens as part of their illness. This is called acute kidney injury (AKI). AKI prevents the kidneys from working properly, causing more acid than normal to build-up in the blood (a process known as acidosis) which can cause further harm. Once this point has been reached, more than half of patients who have acidosis and AKI will not survive their illness. _x000D_ _x000D_ One way to treat patients with acidosis is to give patients an alkali (opposite to acid) to stop the effects of the acid build-up and to bring the level of acid in the blood to normal. Sodium bicarbonate is often used and is a cheap and accessible treatment, but there is little evidence to support its use, which has resulted in variation in practice with some doctors using it, and others not. Doctors and nurses have to decide if the patient should get sodium bicarbonate or progress to more invasive kidney support (known as renal replacement therapy, RRT), which has added risks and needs specialist staff and equipment, making it very expensive._x000D_ _x000D_ So far, only one study has looked at the benefits of sodium bicarbonate in critically ill patients with acidosis. This found that giving sodium bicarbonate to all patients who had acidosis was not an effective treatment. However, in a subgroup of patients who had acidosis and AKI, results pointed to possible benefits of sodium bicarbonate, with fewer patients dying and fewer patients needing RRT. However, to know with certainty, this needs to be tested thoroughly in a larger study (known as a randomised clinical trial) specifically designed to test this question._x000D_ _x000D_ Our aim is to find out whether using sodium bicarbonate to treat critically ill people with acidosis and AKI improves survival and is cost-effective for the NHS. We plan to conduct a randomised clinical trial, in which we will include 2,250 patents from 60 NHS critical care units. They will be randomly assigned by a computer to receive sodium bicarbonate or no sodium bicarbonate. This helps to ensure that the two groups are as similar as possible, and only differ by whether they receive bicarbonate or not. All other medical treatment will be decided by the doctors and nurses treating the patient. We will follow-up all patients at 28-days, 90-days and 1-year following the study to see how they are after leaving the ICU._x000D_ _x000D_ Giving sodium bicarbonate to critically ill patients with acidosis and AKI may increase the number of patients who survive their illness and may also reduce the need for patients to undergo RRT, which may mean they recover more quickly and may also have important cost implications for the NHS. _x000D_ _x000D_ We have patient and public representatives as co-investigators on this study. They have been involved in the design of the study and how the study will be conducted. They will also help to oversee the conduct and management of the study._x000D_ _x000D_ Once the study is complete, the results will be published in widely read and well-regarded medical journals. The results will also be presented at various national and international conferences for intensive care doctors, nurses, other health professionals, managers and policy makers. We will also make the results available to the public and patients through our website.

Lay abstract: 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]?_x000D_ _x000D_ 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._x000D_ _x000D_ 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._x000D_ _x000D_ Methods: Pragmatic multicentre, open, data-enabled RCT with internal pilot phase and integrated economic evaluation._x000D_ _x000D_ Setting: 60 NHS critical care units participating in the Case Mix Programme (CMP) national clinical audit._x000D_ _x000D_ Population: Critically ill adults with acidosis (pH <7.25, PaCO2 of <6.0 and bicarbonate <=20mmol/l) and AKI (KDIGO stage 2 or 3)._x000D_ _x000D_ Intervention: IV 8.4% sodium bicarbonate aiming to achieve pH >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] _x000D_ _x000D_ Comparator: No IV sodium bicarbonate. _x000D_ _x000D_ 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._x000D_ _x000D_ Timelines for delivery:_x000D_ 01/03/2021 to 31/12/2025 (58 months)_x000D_ _x000D_ 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.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RENAL AND UROGENITAL