| Acronym | eTHoS |
|---|---|
| Number | ISRCTN80061723 |
| Protocol Link | http://www.isrctn.com/ISRCTN80061723 |
| Public Trial Registry Link | http://www.isrctn.com/ISRCTN80061723?q=haemorrhoidopexy%20OR%20hemorrhoidopexy%20&filters=&sort=relevance&offset=4&totalResults=5&page=1&pageSize=10&searchType=basic-search |
| Published Results Link | https://www.ncbi.nlm.nih.gov/pubmed/27726951 |
| Status | Published |
| Category | Proctology |
| Treatment Course | Surgery |
| A pragmatic multcentre randomised controlled trial comparing stapled haemorrhoidopexy to traditional excisional surgery for haemorrhoidal disease in patients with circumferential haemorrhoids grade II to IV. The primary clinical and economic outcomes are QoL profile (area under the curve derived from the EuroQol Group's 5 Dimension Health Status Questionnaire (EQ-5D) at all assessment points and incremental cost per quality adjusted life year (QALY) based on the responses to the EQ-5D at 24 mont |
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Angus J M Watson Professor |
| Profile Link |
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Centre for Healthcare Randomised Trials (CHaRT) University of Aberdeen, Health Services Research Unit, Health Sciences Building, Foresterhill Aberdeen ABERDEEN UK |
| Website |
| 1. Raigmore Hospital Old Perth Rd Inverness IV2 3UJ UK Contact: 01463 704000 (switchboard) Website |
| 2. Aberdeen Royal Infirmary Foresterhill Rd Aberdeen AB25 2ZN UK Contact: 0345 456 6000 / If calling from abroad, then dial 00 44 345 456 6000 Website |
| 3. University Hospital of North Tees Hardwick Road Stockton-on-Tees TS19 8PE UK Contact: 01642 617617 Website |
| 4. Northern General Hospital Herries Road Sheffield S5 7AU South Yorkshire Contact: 0114 243 4343 Website |
| 5. Royal Sussex County Hospital Barry Building, Eastern Rd Brighton BN2 5BE UK Website |
| 6. Croydon University Hospital 530 London Road Croydon CR7 7YE UK Website |
| 7. James Cook University Hospital Marton Road Middlesbrough TS4 3BW UK Website |
| 8. Darlington & Durham NHS Trust Dr Piper House/King Street Darlington DL3 6JL UK Website |
| 9. Royal Derby Hospital Uttoxeter Road Derby DE22 3NE UK Website |
| 10. Forth Valley Royal Hospital Stirling Road Larbert FK5 4WR UK Website |
| 11. Hillingdon Hospital Pield Heath Road Uxbridge UB8 3NN UK Website |
| 12. Huddersfield Royal Infirmary Acre St, Lindley Huddersfield HD3 3EA UK Website |
| 13. Pinderfields General Hospital Aberford Road Wakefield WF1 4DG UK Website |
| 14. Manchester Royal Infirmary Grafton Street Manchester M13 9WL UK Website |
| 15. Glan Clwyd Hospital Rhuddlan Road, Bodelwyddan Rhyl LL18 5UJ UK Website |
| 16. John Radcliffe Hospital Headley Way, Headington Oxford OX3 9DU UK Website |
| 17. Royal Cornwall Hospital 2 Penventinnie Lane, Treliske Truro TR1 3LQ UK Website |
| 18. Lincoln County Hospital Greetwell Road Lincoln LN2 5QY UK Website |
| 19. Norfolk and Norwich University Hospital Colney Lane Norwich NR4 7UY UK Website |
| 20. Chelsea and Westminster Hospital 369 Fulham Road, Chelsea London SW10 9NH UK Website |
| 1. The National Institute for Health Research (NIHR), Health Technology Assessment (HTA) Programme 08.24.2002 |
| 2. University of Aberdeen (co-sponsors) |
| Objective: | Full details for the trial protocol including references can be found at: http://www.trialsjournal.com/content/15/1/439 Haemorrhoids are common in all age groups from mid-teens onwards. In 2006 and 2007, approximately 25,000 haemorrhoidal procedures were performed in England as hospital day-case or inpatient admissions, resulting in significant calls on health service resources. The treatment of haemorrhoidal disease is directed at relieving its related symptoms. Traditional surgical haemorrhoidectomy (TH) involves excision of the haemorrhoidal cushions and is generally advocated for symptomatic haemorrhoids of grade III or IV. This traditional approach, whilst effective, is however associated with severe pain. Stapled haemorrhoidopexy (SH) was conceived over 15 years ago and was first described by Longo [Longo A: Treatment of haemorrhoidal disease by reduction of mucosa and haemorrhoidal prolapse with a circular suturing device: a new procedure, unpublished]. Its potential advantages over traditional surgery include a reduction of operating time, hospital stay, time to return to work and postoperative pain. These features would seem to make it attractive to patients and healthcare providers. Nevertheless, uncertainties around complication rates, recurrence of symptoms and costs preclude its widespread use across the National Health Service (NHS). The decision to evaluate clinical and cost-effectiveness of the two surgical treatments for haemorrhoids (stapled haemorrhoidopexy and traditional haemorrhoidectomy) There have been multiple randomised controlled trials (RCTs) comparing SH with TH. These RCTs have been analysed in two systematic reviews and a Health Technology Assessment (HTA) monograph. The HTA included a review of the clinical effectiveness data from 27 RCTs (n =2,279; 1,137 SH; 1,142 TH). When comparing SH with TH, the authors revealed equivalent complication and pain rates at day 21. However, SH patients had less pain in the immediate post-operative period compared with TH. Over the longer term, there was a significantly increased rate of residual prolapse requiring re-intervention with SH; however, there was no evidence of a difference in the number of patients experiencing pain or bleeding between SH and TH. The economic evaluations of the two interventions reported in the HTA monograph found that TH dominated SH, but it should be noted that TH and SH had very similar costs and Quality of Adjusted Life Years (QALYs). The additional cost of the stapling instrument was largely, but not completely, offset by savings in operating time and hospital stay. In terms of QALYs, the improvements in quality of life due to lower pain levels in the early post-operative period with SH were offset by losses in quality of life as a result of the higher rate of symptoms over the follow-up period. SH thus appears to be associated with less pain in the immediate postoperative period, but a higher rate of recurrence in the longer term and increased need for further surgery. These findings are based on data from small trials, all with methodological flaws, and providing limited data on quality of life (or with respect to an economic interpretation, health state utilities) in the early postoperative period. The study by Thaha and colleagues reported similar findings. There are, however, a number of potential limiting factors in the applicability of this study. First, the SF-36 data used to measure quality of life did not rule out substantial differences, which only a larger trial would be able to detect. Second, the stapling gun has subsequently undergone refinement (recruitment was completed in 2002). Third, the trial was conducted prior to the stapling technique being well-established in the UK health care system. Whilst there is a reasonable volume of work on grade III and IV haemorrhoids, there is a paucity of clinical and economic data regarding SH or TH for grade II haemorrhoids. Our group has conducted a RCT comparing rubber band ligation (RBL) with SH for grade II haemorrhoids using both clinical and economic outcomes. This showed a superior clinical effect of SH compared to RBL in terms of recurrence of haemorrhoid symptoms. However from a health economic standpoint, SH, when compared with RBL could not be justified, even with a two-year follow-up. The trend over a longer period, however, suggested that the greater failure rate for RBL may eventually reach a level that justified the increased cost of SH. However, a larger trial with longer term follow-up is needed to confirm this. This small trial used similar outcome measures to those being used in eTHoS and had a high return rate over a median follow-up period of 36 months. Internal reproducibility of the symptom score (the Haemorrhoid Symptom Score) was also validated in this trial by re-administration of questionnaires after an appropriate wash-out period. This symptom score measures the presence, frequency and severity of key haemorrhoidal symptoms (prolapse, pain, bleeding, pruritis, seepage and incontinence for flatus or faeces). These symptoms are scored from 0 to 4 in each domain (except for pain, which scores from 0 to 2). The Cleveland incontinence score is a standard measure of the degree of disturbance to life caused by incontinence. While it is evident that many patients with haemorrhoids have mild disturbance mainly related to flatus, the main utility is in detecting any problems related to sphincter injury as a result of surgery. There is, therefore, a need for an adequately powered, high quality, multicentre RCT comparing the clinical and cost-effectiveness of SH compared with TH. Patient reported health status will be observed over the trial period as well as symptoms related to haemorrhoids, general health and complications from either procedure. The primary objective is to compare patient reported overall health related quality of life (measured using the EQ-5D) over a period of 24 months. The secondary objectives are to compare sub-domains of health (SF-36 scores, pain and symptoms), disease recurrence, complication rates, and direct and indirect costs to the NHS, and cost-effectiveness (measured in terms of incremental cost per QALY, where QALYs are derived from responses to the EQ-5D). |
| Aim: | The aim of eTHoS is to assess whether SH is more effective and cost-effective compared with traditional excisional haemorrhoidectomy (TH) for people with haemorrhoids (grade II, III and IV). |
| Methods: | eTHoS is a pragmatic, multicentre, superiority, parallel group trial comparing SH and TH. People considered for trial entry Inclusion criteria include the following: 1. patients with circumferential haemorrhoids grade ii, grade iii and iv, 2. patients aged 18 years or older and 3. written informed consent. Exclusion criteria include the following: 1. previous surgery for haemorrhoids (traditional or stapled) (except rubber band ligation (rbl) or haemorrhoidal artery ligation operation (halo)); 2. previous surgical treatment for anal sphincter injury repair, or symptomatic incontinence and peri-anal sepsis; 3. known inflammatory bowel disease; 4. malignant gastrointestinal disease, within the last five years; 5. medically unfit for surgery or for completion of the trial; or 6. pregnant women. Eligible patients were identified in the clinic setting by the colorectal surgeon or a suitably qualified trained member of the local clinical team. The colorectal surgeon informed the patient during this initial consultation about the different treatments available for their condition as well as giving information about the eTHoS study. As is normal clinical practice, the colorectal surgeon explained the risks and benefits of all the treatment options. Informed consent was obtained from all participants. The colorectal surgeon, or local trained clinical team member, gave each potential participant the Patient Information Sheet. This explained the rationale behind the eTHoS study, as well as what taking part encompassed. Patients who were able to make a decision to join the study whilst they are at the clinic were provided with the eTHoS participant baseline questionnaire that comprises the EQ-5D, SF-36, Cleveland Incontinence Score and Haemorrhoids Symptom Score. Contact details of both the local and central team were provided on the Patient Information Sheet. Patients who required more time to consider participation in the study were encouraged to contact either the local or central team if they had any queries for which they would like clarification before they returned to hospital. The potential participant was then be re-approached by a local clinical team member prior to surgery. Following full written consent and baseline data completion, patients were randomised, as near to their surgery as possible, to one of the two study groups in equal proportion using the randomisation application at the trial office. Patients who returned their signed consent forms by post were then complete the baseline questionnaire prior to surgery, to enable randomisation to take place. Participants were randomised to one of the two study groups in equal proportion using a randomisation application in the trial office. This randomisation application was available 24 hours a day, 7 days a week and had both an Interactive Voice Response (IVR) telephone and web-based interface. Randomisation would take place as near to the time of surgery as possible using minimisation. The minimisation algorithm [11] will used centre, grade of haemorrhoidal disease (II, III or IV), baseline EQ-5D score and gender. The eTHoS patient follow-up consisted of a visit to the hospital, approximately 6 weeks after surgery (range allowed 4 to 8 weeks), for a clinical consultation and assessment. At randomisation, both the participant and the surgeon were aware of the treatment randomisation group. Data collected at all participant visits (including the initial consultation/eligibility visit) were recorded in the first instance on paper case report forms (CRFs) then entered onto the trial database via a secure web portal. The trial office will coordinated follow-up and data collection in collaboration with the UK centres. The study web portal held electronic versions of all trial documentation and facilitated communication between study personnel. The surgical form was completed by the operating surgeon. All participant-reported outcomes (PROs) (apart from baseline) were collected by postal questionnaires administered from the trial office. Data on any additional hospital visits were recorded on the CRF completed when participants returned for the 6-week clinical follow-up or in the patient reported outcomes. General practitioners (GP) were notified by letter, which included a GP eTHoS information sheet, that their patient has been randomised to the eTHoS study. GPs were asked to phone the Study Office if the participant moved, become too ill to continue with the study, died, or if any other notifiable event/possible adverse event occurred. Alternatively, staff at the study office may contact the GP. Consent was sought from all participants recruited to the RCT to be flagged for notification of haemorrhoidal recurrence. To evaluate long term safety, the participants were flagged for further haemorrhoidal surgery through Hospital Episode Statistics (HES) in England and Patient Episode Database Wales (PEDW) in Wales and the Information Services Division (ISD) data in Scotland, when all participants had reached 12 and 60 months. We will reported serious adverse events in accordance with the guidance from the National Research Ethics Service (NRES), which is a subdivision of the National Patient Safety Agency. The study had a patient-centred and an economic primary outcome, and multiple secondary patient-reported, clinical and economic outcomes. Primary The patient-centred outcome is the quality of life profile over the follow-up period (area under the curve derived from EQ-5D measurements at baseline, 1 week, 3 weeks, 6 weeks, 12 months, EQ-5D at 18 months only if not completed at 12 months, 24 months and (subject to securing further funding) 60 months. The trial economic outcome is the incremental cost per quality adjusted life year (QALY) gained with QALYs based on the responses to the EQ-5D at 24 months. The economic model outcome is the incremental cost per QALY over the lifetime of the participant. Secondary The patient-reported outcomes include the following: 1. generic health profile measured by SF-36 and EQ-5D, 2. visual analogue scale (VAS) pain score, 3. Cleveland incontinence score, 4. haemorrhoid symptom score, 5. post-operative analgesia consumption, 6. recurrence of haemorrhoids, and 7. tenesmus. Clinical outcomes are perioperative and postoperative complications including the following: 1. haemorrhage, 2. requirement for blood transfusion, 3. anal stenosis, 4. anal fissure, 5. urinary retention (which requires catheterisation), 6. residual anal skin tags, 7. difficult defecation, 8. wound discharge, 9. pelvic sepsis, and 10. pruritus. Economic outcomes will be the costs based on resource use data and include the following: 1. Costs to the NHS and patients at two years a. time to recovery b. length of hospital stay c. use of health services for haemorrhoid related events or treatments d. patient costs (treatments, travel to health services, sick leave) e. need for alternative management for haemorrhoids (for example, surgery, drugs) f. other use of health services i. visits to GP ii. visits to practice nurse iii. visits to colorectal surgeon 2. Estimated lifetime cost to NHS and patient 3. QALYs estimated from the EQ-5D at 24 months 4. QALYs estimated over the patient?s lifetime 5. Cost-effectiveness analysis (incremental cost per case of stapled haemorrhoidopexy and traditional haemorrhoidectomy excision avoided). The full details of the statistical analysis plan (SAP) can be obtained from the Trial Office by contacting ethos@abdn.ac.uk. Study analyses will follow the SAP agreed in advance by the Trial Steering Committee. The main statistical analyses will be based on all participants as randomised, irrespective of subsequent compliance with the treatment allocation. The primary outcome, area under the curve (measured by EQ-5D), will be generated for each participant using the trapezoidal rule. Missing EQ-5D data will be estimated using a multiple imputation approach which makes use of partial outcome data [14]. Sensitivity analyses will be conducted to assess the robustness of the treatment effect estimate to these approaches. The primary outcome measure will be analysed using linear regression with adjustment for the minimisation variables. Secondary outcomes will be analysed using generalised linear models with adjustment for minimisation and baseline variables as appropriate. Statistical significance will be at the two-sided 5% level with corresponding confidence intervals derived. Subgroup analyses will explore the possible treatment effect modification of clinically important factors (grade and gender), through the use of treatment by factor interaction, all using a stricter two-sided 1% level of statistical significance. An independent Data Monitoring Committee (DMC) will meet early in the course of the trial to agree to its terms of reference and will review confidential interim analyses of accumulating data. |
| Reason for International Trial: | eTHoS is the largest multi-centre randomised controlled trial of it's kind and aims to assess whether SH is more effective and cost-effective compared with traditional excisional haemorrhoidectomy (TH) for people with haemorrhoids (grade II, III and IV) as to date, there is limited evidence available. At the end of the recruitment phase the trial achieved a sample size of 777. |