Title: Role of ward based goal-directed fluid therapy (GDFT) in acute pancreatitis: a feasibility randomised controlled trial
Funder: Department of Health and Social Care

Abstract: Design: A pragmatic, two centre, feasibility randomised controlled trial. Target organisations: Royal Free Hospital and Royal London Hospital. Target population: Adults (> 16 years) admitted as an emergency with acute pancreatitis without cardiac failure, and not requiring immediate admission to the intensive therapy unit (ITU). Health technologies assessed: Standard care: The amount and rate of fluid therapy (Hartmann's solution) will be based on the blood pressure, heart rate and urine output. Intervention: Ward based GDFT. GDFT will be carried out for 48 hours after admission, considered the golden period for interventions that may decrease severity of pancreatitis. GDFT will be based on a standard algorithm which uses the stroke volume (SV) derived from non-invasive cardiac output monitoring using the Cheetah NICOM. Rationale: Previous studies have shown that GDFT decreases complications and mortality in people undergoing major surgery and those with systemic inflammatory response syndrome (SIRS) respectively. The only RCT in patients with acute pancreatitis (a small RCT) used blood urea nitrogen (BUN) as the target rather than cardiac output/stroke volume as proposed in this study. This will be the first RCT of ward-based goal-directed therapy (GDFT) in patients with acute pancreatitis using cardiac output/stroke volume as the target and has been made possible by the recent availability of portable non-invasive cardiac output equipment such as the Cheetah NICOM. Blinding: The patients will be blinded to their treatment group. The control group will have 'sham GDFT' in which the cardiac output monitor is attached and routine recordings made by the research team. However the clinical team will not have access to the recordings and will administer fluids as in standard care. Outcome measures: The primary outcome of the trial will be the ability to recruit patients at the selected site (recruitment rate), rate of withdrawal from GDFT protocol, and reasons for withdrawal from GDFT protocol. The secondary outcomes include the following: Mortality, health-related quality of life (HRQoL by EQ5D), treatment-related adverse events and serious adverse events. Proportion of people with severe acute pancreatitis, necrotising pancreatitis, infected pancreatic necrosis, requiring ITU stay, requiring renal replacement therapy, requiring ventilation, requiring surgical interventions for complications related to pancreatitis and incidence of positive blood cultures. Duration of ventilation, length of hospital stay, length of ITU stay, time to return to pre-pancreatitis activities, number of work days lost (in those who work), and costs. C-reactive protein (CRP) (routinely measured clinically). Follow-up and timing of measurement of outcomes: Participants will be followed for 90 days. All clinical outcomes will be measured on 2 days, 7 days, 30 days, 60 days, and 90 days by face-to-face or telephone follow-up. CRP will be measured at 24 hours and 48 hours and every 24 hours during the hospital stay as per routine clinical practice. Sample size The aim of this study is to assess the feasibility of ward based GDFT in patients with acute pancreatitis and to inform the design and sample size of a subsequent large multi-centre prospective randomised controlled trial. A convenient sample size of 50 patients, randomised equally to the two groups, has been chosen for this feasibility study. Recruitment 50 participants over 17 months (30% recruitment rate). Project time-table Total duration: 28 months (set-up: 4 months, recruitment: 17 months; follow-up: 3 months; analysis: 4 months). Expertise in team: Surgeons, intensivist, patient representative, statistician, clinical trials unit, qualitative researcher, health economist.

Lay abstract: The pancreas helps digest food and control sugar in our blood. Acute pancreatitis affects 18,000 people in the UK every year and 6% die. The pancreas swells and releases chemicals into blood vessels which then leak; vital organs e.g. heart and kidneys don t get enough oxygen and may stop working. Treatment involves replacing salts and fluids but there is disagreement about how to provide the right amount of fluid. Too little and the kidneys and other organs may fail, but too much can lead to lung and heart failure. The amount of fluid given is calculated using the patient s pulse rate, blood pressure, and urine produced. In goal directed fluid therapy (GDFT), the amount is calculated by a machine measuring oxygen in the blood and blood pumped by the heart. GDFT is used in intensive care units, not wards, because special tubes need to be inserted into neck veins. Portable machines that don t require these tubes are available but are expensive and require specially trained medical staff. Most damage caused to the body from acute pancreatitis happens within the first 48 hours. This trial will look at the possibility of giving fluids using the portable GDFT machine for the first 48 hours to patients admitted with acute pancreatitis. After 48 hours we will provide standard fluid therapy based on usual measures. 50 patients will take part in this study and be followed for 3 months. Half will have the amount of fluids calculated in the normal way, and half using a GDFT machine. Participants in each group will be chosen by chance, not by the doctor or patient deciding. This study looks at the practicality and safety of using GDFT on wards to treat acute pancreatitis and will help design a larger trial to investigate effectiveness and value for money.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL