Clinical trial NCT04101773: Napoleon Trial: Optimal Treatment for Recurrent Haemorrhoidal Disease
Official title: Cost-effectiveness and Effectiveness of Rubber Band Ligation Versus Sutured Mucopexy Versus Haemorrhoidectomy in Patients With Recurrent Haemorrhoidal Disease: a Multicentre,Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hemorrhoids
Keywords: hemorrhoids
haemorrhoidal disease
recurrence
rubber band ligation
haemorrhoidectomy
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2019-09-24
Enrollment: 558
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective multicentre randomized controlled trial.
Primary purpose: TREATMENT

Brief summary: Rationale: There is level I evidence in literature that the first management step of HD is basic treatment, including laxatives and high fibre dieti, ii. The next treatment modality after basic treatment in case of persistent symptoms is rubber band ligation (RBL), which can be repeated if necessary.

There is currently no consensus and a lack of evidence regarding the best treatment option for these patients having recurrent HD: continuing RBL or a surgical intervention. Furthermore, there is no estimate of costs and cost-effectiveness in this patient group.

Objective: The primary objective of this RCT is to compare the effectiveness of RBL, sutured mucopexy and haemorrhoidectomy regarding recurrence and patient-reported symptoms for recurrent grade 2 and 3 HD after at least 2 previous RBL treatments. Secondary objectives are to compare RBL, sutured mucopexy and haemorrhoidectomy for recurrent grade 2 and 3 HD after previous RBL treatments in terms of early and late complications, impact of symptoms on daily activities, patient satisfaction with treatment, health-related quality of life, costs and cost-effectiveness, and budget impact.

Study design: Dutch prospective multicentre randomized controlled trial.

Study population: Patients ≥18 who have recurrent grade 2 or 3 haemorrhoidal disease and who had at least 2 rubber band ligation treatments. In total, 558 patients will be included.

Intervention: Rubber band ligation versus sutured mucopexy versus haemorrhoidectomy. All three interventions are part of Dutch usual care, and serve as each other's control.

Main study parameters/endpoints: Primary outcomes are (1) recurrence and (2) patient-reported symptoms assessed after 12 months. Secondary outcome variables are early and late complications, impact of symptoms on daily activities, patient satisfaction with treatment, health-related quality of life, costs, cost-effectiveness and budget-impact.

Detailed description: Haemorrhoidal disease (HD) is the most common type of anorectal complaint in the Netherlands, with an annual prevalence of 10% in general practice. There is level I evidence in literature that the first management step of HD is basic treatment,including laxatives and high fibre diet. The general practitioner usually offers basic treatment. If basic treatment fails patients are referred to the hospital. About 50.000 patients are referred to a hospital for HD in the Netherlands annually. The next treatment modality after basic treatment in case of persistent symptoms is rubber band ligation (RBL), which can be repeated if necessary. RBL is an easy, cheap and outpatient-based procedure. Thirty per cent of the patients, approximately 15.000 patients a year, develop recurrent symptoms after basic treatment and repeat RBL. There is currently no consensus and a lack of evidence regarding the best treatment option for these patients having recurrent HD: continuing RBL or a surgical intervention. Literature indicates that haemorrhoidectomy is the surgical treatment of choice based on outcomes like recurrencerate. The major drawback of this technique is that it is very painful and more costly compared to RBL. A relatively novel, but regular surgical alternative is the sutured mucopexy. Although hospital costs of sutured mucopexy are comparable to haemorrhoidectomy, the operation is less painful and requires less recuperation time. The recurrence rate of sutured mucopexy is ranked between that of RBL and haemorrhoidectomy.

A Dutch national survey conducted by our research group evaluating the management practices of HD demonstrated considerable variation in the best (surgical) treatment option regarding recurrent HD, resulting in potentially undesirable practice variation. The treatment of recurrent grade 2 or 3 HD currently depends on the preference and the experience of the surgeon and of the patient, without high level evidence substantiating this practice variation. This implies a need for a high quality study regarding the treatment of recurrent grade 2 or 3 HD. Diminishing this practice variation will endorse cost-effectiveness in healthcare settings.To our knowledge, this will be the first RCT worldwide comparing RBL, sutured mucopexy and haemorrhoidectomy in recurrent grade 2 or 3 HD and generating high-level evidence of the (cost-) effectiveness. The investigators consider combining 2 trials in one with a direct comparison between these three interventions to be an efficient research approach.

Up till now, trials were mostly powered on traditional outcomes like recurrence, a definition that differs widely between studies.To improve transparency between studies and facilitate the ability to compare and combine (future) studies, our research group developed a European Society of Coloproctology (ESCP) Core Outcome Set (COS) for HD. This international COS for HD selected 'patient-reported symptoms' as primary outcome. Additionally, the investigators recently developed a patient reported symptom score for HD: the PROM-HISS. This PROM is based on most cited symptoms in literature and patient interviews. The patient advisory board (PAB) of this project underlines the clinical relevance of this PROM. As the PROM-HISS has not yet been used in other studies and has to be validated, the investigators will additionally use patient-reported symptoms assessed by the PROM-HISS, next to recurrence, as primary outcome in this trial.

Eligibility criteria: Inclusion Criteria:

* Men and women aged 18 years or older
* Recurrent grade 2 or 3 HD
* Patients underwent at least 2 RBL treatments in the last 3 years based on hospital electronic patient file (EPD)
* Eligible for e-mail questionnaires
* Sufficient understanding of the Dutch written language (reading and writing)
* Obtained written informed consent

Exclusion Criteria:

* Previous rectal or anal surgery with the exception of rubber band ligation
* Patients that have had previous surgery treatment for HD (at any time)
* Previous rectal radiation
* Pre-existing sphincter injury
* Pathologies of the colon and rectum
* Medically unfit for surgery or for completion of the trial (ASA\>III)
* Pregnancy
* Patients with hypercoagulability disorders
* Patients using Warfarin or Clopidogrel or oral anticoagulance therapy
* Patients that are unable to give full informed consent

Primary outcomes:
measure: Recurrence
timeFrame: Assessed after 12 months post-intervention.
measure: Patient-reported symptoms measured with the PROM-HISS
timeFrame: The PROM-HISS will be completed by e-mail at four moments during follow-up: (1) at baseline; (2) 7 days; (3) 6 weeks; and (4) 12 months post-procedure.
Secondary outcomes:
measure: Early complication(s) - Abscess
timeFrame: This outcome measure will be assessed within 7 days post-procedure.
measure: Impact of symptoms on daily life and patient satisfaction with treatment
timeFrame: The PROM-HISS will be completed by e-mail at four moments during follow-up: (1) at baseline; (2) 7 days; (3) 6 weeks; and (4) 12 months post-procedure.
measure: Health Related Quality of Life
timeFrame: The PROM-HISS will be completed by e-mail at four moments during follow-up: (1) at baseline; (2) 7 days; (3) 6 weeks; and (4) 12 months post-procedure.
measure: Early complication(s) - Urinary retention
timeFrame: This outcome measure will be assessed within 7 days post-procedure.
measure: Late complication(s) - Incontinence
timeFrame: Incontinence will be assessed at 52 weeks (1 year) post-procedure.
measure: Late complication(s) - Anal stenosis
timeFrame: Anal stenosis will be assessed at 52 weeks (1 year) post-procedure.
measure: Late complication(s) - Fistula
timeFrame: Fistula will be assessed at 52 weeks (1 year) post-procedure.
measure: Costs
timeFrame: The questionnaires will be filled out at baseline, 6 weeks and 12 months follow-up.
measure: Cost-effectiveness
timeFrame: The EQ-5D-5L will be administered at baseline, 1 week, 6 weeks and at 12 months follow-up.
measure: Budget Impact Analysis
timeFrame: Time horizon of 5 years.
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Capelle Aan Den IJssel
country: Netherlands
facility: IJsselland Ziekenhuis
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis
city: Helmond
country: Netherlands
facility: Elkerliek Ziekenhuis
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Roermond
country: Netherlands
facility: Laurentius Ziekenhuis
city: Utrecht
country: Netherlands
facility: Diakonessenhuis
city: Veldhoven
country: Netherlands
facility: Máxima Medisch Centrum
city: Venlo
country: Netherlands
facility: VieCurie Medisch Centrum
Study officials:
affiliation: Maastricht University Medical Centre
name: Stephanie Breukink, MD PhD
role: STUDY_CHAIR
References:
citation: Kuiper SZ, Dirksen CD, Kimman ML, Van Kuijk SMJ, Van Tol RR, Muris JWM, Watson AJM, Maessen JMC, Melenhorst J, Breukink SO; Napoleon Trial Study Group. Effectiveness and cost-effectiveness of rubber band ligation versus sutured mucopexy versus haemorrhoidectomy in patients with recurrent haemorrhoidal disease (Napoleon trial): Study protocol for a multicentre randomized controlled trial. Contemp Clin Trials. 2020 Dec;99:106177. doi: 10.1016/j.cct.2020.106177. Epub 2020 Oct 17.