Title: RadiO fRequency ablatION for haemorrhoids (ORION)
Funder: Department of Health and Social Care

Abstract: Piles are very common. In many people once other causes have been excluded the symptoms respond to simple treatments such as eating better and not straining on the toilet. In some the symptoms are really bad or carry on despite these changes in the way people lead their lives. Some form of treatment is needed and in a few this may be surgery. _x000D_ _x000D_ Whilst a surgeon may offer many types of operation none are perfect. Some may be good at curing the piles but may cause pain or damage to the body. Others may be less painful but the piles may come back. Many ‘newer’ treatments cost a lot. If these newer treatments are as good as the current treatments but are easier for the patient (maybe less painful, no need to go to sleep to have the operation, quicker return to normal life, safer) then they may be worth paying for._x000D_ _x000D_ There is a new treatment for piles called radiofrequency ablation. This uses radio waves to destroy the pile. According to the small amount of testing that has been done, it is safe, there is only a little pain and people get over the surgery quickly. It also seems to be as good as other operations in curing the piles. The trouble is the new surgery has not been tested enough for us to be sure it is as good as some people say it is and it costs a lot. We need to carefully find a way of testing to see if the new surgery is at least as good as the other surgeries in curing piles and whether it is easier for the patient to get over in order to allow the NHS to spend money on it being used. _x000D_ _x000D_ To do such a test we have to pick patients who a surgeon feels need surgery for their piles. These people will have the study explained to them and, only if they are happy to be involved, they will be selected by entirely by chance to have one of either the new radiofrequency ablation surgery or whatever the surgeon feels is the best other surgery. These other surgeries are one of haemorrhoidectomy (cut out the pile), stapled haemorrhoidopexy (pull up the piles into the bowel) or haemorrhoidal artery ligation (tie off the blood supply). The usual care operation will be made known to the patient and explained along with the radio frequency operation. However, once randomisation has occurred and the operation done we are proposing that the patient will not be told whether they have had this 'usual operation' or the radio frequency ablation. _x000D_ _x000D_ We have asked patients to help us with what we can ask to see if people are better after surgery. Most felt asking whether the piles have all gone and stay gone was the best thing to ask. They also told us to ask about pain, how quickly people got over the surgery if it caused any harm and how much it cost. If the new surgery cures piles the same as the other surgeries but is less painful and easier for the patient and is not too costly then we can say that it should be done in the NHS.

Lay abstract: DESIGN_x000D_ Pragmatic multicentre patient/ assessor blind parallel group individual participant-randomised (1:1 allocation) randomised controlled trial._x000D_ SETTING_x000D_ 16 UK NHS hospitals._x000D_ POPULATION_x000D_ Patients with symptomatic grade II/III haemorrhoids who qualify for operative intervention (both groups failed conservative treatment +grade II haemorrhoids have failed at least one episode of rubber band ligation)_x000D_ INTERVENTIONS_x000D_ Radiofrequency ablation vs. surgeons choice of haemorrhoidectomy, haemorrhoidal artery ligation or stapled haemorrhoidopexy (in line with current international guidelines). Patients blinded to operation as both procedures done under GA + complications are similar across interventions. Adequacy of blinding will be checked by asking participants to guess which treatment they received. Assessors also blinded to intervention – no visualisation of surgical site is required._x000D_ OUTCOMES._x000D_ Primary outcomes_x000D_ 1. Recurrence @ 12 months post procedure (defined according to definition for HubBLe trial)_x000D_ 2. Pain over 7 days post procedure_x000D_ Secondary outcomes_x000D_ 1. Pain score @21 days, 6 wks_x000D_ 2. Days of work lost_x000D_ 3. Recurrence @ 6 wks_x000D_ 4. Haemorrhoid severity score_x000D_ 5. EQ-5D-5L @baseline, 1,7,21 days, 6 wks, 1 yr_x000D_ 6. Vaizey continence score @baseline, 6 wks, 1 yr_x000D_ 7. Health and social care resource use @ 6 wks, 1 yr_x000D_ 8. Complications_x000D_ 9. Cost_x000D_ SAMPLE SIZE_x000D_ For this intervention to be acceptable for NHS practice, it cannot be significantly worse than current options in terms of recurrence. For the intervention to be acceptable to patients, it should also bring the benefit of less pain, otherwise it cannot offer benefit over current options. To this end, we have based our sample size on two co-primary endpoints: i) a non -inferiority design for recurrence and ii) but superiority design for pain over 7 days._x000D_ We propose a trial which recruits 376 participants (188 per arm). Assuming a 15% drop out, a cluster effect (ICC) of 1% among 15 surgeons, a one year recurrence rate of 15% and usual care rate of 20%, we will have 90% power to demonstrate non-inferiority to within 10% at the one-sided 2.5% significance level. Previous trials with VAS pain outcomes data reported standard deviations between 2.4 to 2.7 units: the trial has a power >90% to detect a 1 unit change if the standard deviation is within this range and the pre-post correlation is 0.4. _x000D_ HEALTH ECONOMICS_x000D_ The health economic analysis will calculate the incremental cost per quality adjusted life year (QALY) of radiofrequency ablation for the treatment of piles compared to standard NHS practice. This will consist of a within trial analysis over a one year period._x000D_ PROJECT TIMETABLE _x000D_ 43-month study._x000D_ m1-m8 Set-up_x000D_ m9-m23 Recruitment at 16 centres_x000D_ m9-m15 Internal pilot_x000D_ m23-m25 Surgical wait time for last participant_x000D_ M23-m37 12m follow-up for last participant_x000D_ M38-m43 Analysis +write-up_x000D_ Internal pilot will aim to recruit 124 participants with 83 as a minimum for continuation . _x000D_ ELIGIBILITY CRITERIA_x000D_ Consenting adults >18y.o, fit for general/regional anaesthetic, grade II/ III haemorrhoids, failed conservative therapy. Exclusions: pregnancy, other anorectal +colonic causes of symptoms, immunodeficiency, concurrent anticoagulants, contraindication to general or spinal anaesthetic, inability to consent. _x000D_ COMPLEMENTARY SKILLS_x000D_ Clinical, methodological statistical skills +patient experience. Delivered on similar trial (HuBBle) on time and in budget

Research activity codes: 6.4 SURGERY;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: ORAL AND GASTROINTESTINAL