Title: Salbutamol for analgesia in renal colic: A prospective, randomised, placebo controlled phase II trial
Funder: Department of Health and Social Care

Abstract: Research question Does the addition of salbutamol to the standard analgesic regime result in improved pain relief for patients with confirmed renal colic when compared to the standard analgesic regime plus placebo? Background Renal colic is the pain experienced by a patient when a renal calculus (kidney stone) causes partial or complete obstruction of part of the renal outflow tract. Lifetime incidence is approximately 10%. The standard analgesic regimes for renal colic are often ineffective and associated with significant side effects. Pain in renal colic is caused by ureteral spasm and subsequent inflammation. Beta agonists, such as salbutamol, have been shown to cause ureteral relaxation and therefore may reduce pain. Primary Aim To explore whether salbutamol is an efficacious analgesic adjunct when added to the standard analgesic regime for patients presenting to the ED with confirmed renal colic. Primary outcome The difference in the change in pain scores (measured on an 100mm Visual Analogue Scale) from baseline to 30 minutes post drug administration between trial arms in patients with confirmed renal colic. Methods We propose a phase II single centre randomised controlled trial investigating the potential efficacy of salbutamol as an analgesic adjunct in patients with confirmed renal colic. Emergency department adult patients with suspected renal colic and severe pain will be randomised to receive either intravenous salbutamol or placebo in addition to conventional analgesia. Pain scores (VAS and short-form McGill Pain Questionnaire) will be recorded for up to 24 hours. A variety of secondary outcomes and feasibility data will be collected to inform a subsequent phase III trial. Timelines for delivery Run-in Phase (August 2018 - June 2019) Contracts signed, committees meeting, study documents approved, applications to HRA/REC/MHRA submitted. Set-up Phase (April - June 2019) Milestone 01/07/2019: Grant Activation Recruitment Phase (July 2019 - April 2021) Milestone 30/04/2021: Completion of recruitment. Close-out Phase (May- October 2021) Milestone August 2021: Data analysis complete Milestone 31/10/2021: Report delivered to RfPB. Manuscript and abstracts submitted. HTA application for funding for the phase III trial submitted and under review. Anticipated Impact and Dissemination The findings of this study will be disseminated in a variety of formats to improve accessibility to the medical community, patients and society. Publication in an international high impact medical journal Presented at national and international emergency medicine and urology conferences Presented in online fora including podcasts and blogs Dissemination social media channels PPI representatives will assist with dissemination of findings. This phase II trial will not directly impact patient care, but has the potential to lead to a phase III trial, the results of which will be available within 5 years of completion. If the phase III trial demonstrates efficacy then possible impacts for patients with renal colic include: Improved Analgesia Reduced time to pain relief Improved analgesic side effect profile Reduced staff burden Reduced hospital admissions and length of stay

Lay abstract: Kidney stones can become stuck in the ureter (the tube between the kidney and the bladder). This is called renal colic and is very painful. Patients with renal colic often attend the Emergency Department due to pain. Traditional painkillers are only partly effective in reducing this pain, and have side effects such as being sick and sleepiness. There is evidence that salbutamol (a drug used to treat asthma) relaxes the human ureter. We believe this may reduce the pain associated with kidney stones but there have been no studies in humans to demonstrate this effect. We know that salbutamol is a very safe drug. It has been used for a long time in the treatment of asthma. Patients attending the emergency department with suspected kidney stones will be given the chance to take part in the study. If they agree, they will be randomly chosen to receive either salbutamol (the active drug) or placebo (a &ldquo;dummy&rdquo; drug e.g. water) as an injection into a drip. Neither the patient nor the treating doctor will know which drug was given. We will collect information about patients pain levels over the following 24 hours. Patients will still be given all normal pain relief, both on their arrival and during their time in hospital. This is the first trial investigating this treatment for renal colic so we are conducting a small study of approximately 120 patients suspected to have the condition in the emergency department. The main aim is to see if salbutamol has any effect on the pain caused by kidney stones. Patients who have suffered from renal colic have helped design this research study and have agreed that we need better treatments for renal colic pain. The results of this research will be published in a medical journal and presented at conferences. They will be made available to patient groups and the general public using patient representative networks. Most importantly, the results of this study will help with the design of a further, much larger research project to prove whether salbutamol is an effective pain killer for patients with renal colic.

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