Napoleon Trial: Optimal Treatment for Recurrent Haemorrhoidal Disease

NCT ID: NCT04101773

Last Updated: 2019-09-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 558 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-01
• Study Completion Date: 2023-03-01

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.

Conditions

Hemorrhoids

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Rubber Band Ligation (RBL)

RBL is generallya simple, inexpensive procedure. It entails a ligation of haemorrhoids using rubber bands. In RBL, a disposable suction device applies a rubber band at least 2 cm proximal to the dentate line at the base of each haemorrhoidal cushion by using an anoscope. The banding process causes necrosis of the banded tissue and slough. The resultant inflammatory reaction causes refixation of the mucosa to the underlying tissue, helping to eliminate haemorrhoidal prolapse.The end result is a return of the haemorrhoidal cushions to a more normal size and configuration, with resolution of haemorrhoidal symptoms.

Group Type: OTHER

RBL versus sutured mucopexy versus haemorrhoidectomy.

Intervention Type: PROCEDURE

All 3 interventions are part of Dutch usual care, and serve as each other's control.

Sutured mucopexy

A sutured mucopexy is an operation performed under general anaesthesia. At 4 cm proximal of the dentate line, a Z- shaped stitch through the rectal wall is placed and then at the upper level of the haemorrhoidal tissue, pulling up the prolapsing haemorrhoid high into the anal canal.

Group Type: OTHER

RBL versus sutured mucopexy versus haemorrhoidectomy.

Intervention Type: PROCEDURE

All 3 interventions are part of Dutch usual care, and serve as each other's control.

Haemorrhoidectomy

Haemorrhoidectomy involves excision of the haemorrhoidal tissue. An elliptical incision is made in the external haemorrhoidal tissue extending proximally through the dentate line to the upper limit of the haemorrhoids. The base of the haemorrhoidal complex is ligated and the haemorrhoid is excised.

Group Type: OTHER

RBL versus sutured mucopexy versus haemorrhoidectomy.

Intervention Type: PROCEDURE

All 3 interventions are part of Dutch usual care, and serve as each other's control.

Interventions

RBL versus sutured mucopexy versus haemorrhoidectomy.

All 3 interventions are part of Dutch usual care, and serve as each other's control.

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephanie Breukink, MD PhD

Role: STUDY_CHAIR

Maastricht University Medical Centre

Locations

Maastricht University Medical Centre

Maastricht, Limburg, Netherlands

Ziekenhuisgroep Twente

Almelo, , Netherlands

Meander Medisch Centrum

Amersfoort, , Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Gelre Ziekenhuizen

Apeldoorn, , Netherlands

Rijnstate Ziekenhuis

Arnhem, , Netherlands

IJsselland Ziekenhuis

Capelle aan den IJssel, , Netherlands

Reinier de Graaf Gasthuis

Delft, , Netherlands

Groene Hart Ziekenhuis

Gouda, , Netherlands

Elkerliek Ziekenhuis

Helmond, , Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

Canisius Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Laurentius Ziekenhuis

Roermond, , Netherlands

Diakonessenhuis

Utrecht, , Netherlands

Máxima Medisch Centrum

Veldhoven, , Netherlands

VieCurie Medisch Centrum

Venlo, , Netherlands

Countries

Netherlands

Central Contacts

Sara Kuiper, MD

Role: CONTACT

s.kuiper@maastrichtuniversity.nl

+31(0)626731279

Facility Contacts

Sara Kuiper, MD

Role: primary

s.kuiper@maastrichtuniversity.nl

+31(0)626731279

Stephanie Breukink, MD PhD

Role: backup

s.breukink@mumc.nl

+31(0)43-3872807

Lutke Holzink

Role: primary

Consten

Role: primary

DeCastro

Role: primary

Duijvendijk

Role: primary

Vening

Role: primary

Doornebosch

Role: primary

Dekker

Role: primary

Baeten

Role: primary

Schipper

Role: primary

Koopal

Role: primary

Hansson

Role: primary

Heemskerk

Role: primary

Pronk

Role: primary

Dielen

Role: primary

Vogelaar

Role: primary

References

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.

Reference Type: DERIVED

PMID: 33080380 (View on PubMed)

Related Links

https://www.escp.eu.com/images/guidelines/documents/ESCP-Core-Outcome_Set-for-haemorrhoidal-disease-Tol_et_al-2019-Colorectal_Disease.pdf

ESCP Core Outcome Set for Haemorroidal Disease

https://www.escp.eu.com/images/guidelines/documents/ESCP-Guidelines-Haemorrhoidal-Disease-2019-02.pdf

ESCP Guideline for Haemorroidal Disease

Other Identifiers

852002023

Identifier Type: -

Identifier Source: org_study_id