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Napoleon Trial: Optimal Treatment for Recurrent Haemorrhoidal Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04101773
Recruitment Status : Not yet recruiting
First Posted : September 24, 2019
Last Update Posted : September 24, 2019
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Maastricht University Medical Center

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.


Condition or disease Intervention/treatment Phase
Hemorrhoids Procedure: RBL versus sutured mucopexy versus haemorrhoidectomy. Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 558 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective multicentre randomized controlled trial.
Masking: Single (Outcomes Assessor)
Masking Description: Due to the comparison of outpatient-based and surgical treatment strategies in this study, blinding to the treatment allocation for patients and medical staff is not possible. The trial statistician will be blinded for the treatment allocation.
Primary Purpose: Treatment
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
Estimated Study Start Date : March 1, 2020
Estimated Primary Completion Date : March 1, 2023
Estimated Study Completion Date : March 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemorrhoids

Arm Intervention/treatment
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.
Procedure: RBL versus sutured mucopexy versus haemorrhoidectomy.
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.
Procedure: RBL versus sutured mucopexy versus haemorrhoidectomy.
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.
Procedure: RBL versus sutured mucopexy versus haemorrhoidectomy.
All 3 interventions are part of Dutch usual care, and serve as each other's control.




Primary Outcome Measures :
  1. Recurrence [ Time Frame: Assessed after 12 months post-intervention. ]
    The definition of recurrent HD is: "unchanged or worse symptoms of HD compared with before starting treatment".

  2. Patient-reported symptoms measured with the PROM-HISS [ Time Frame: 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. ]
    The Patient-Reported Outcome Measure-Haemorrhoidal Impact and Satisfaction Score (PROM-HISS) is a newly developed questionnaire assessing the symptoms of haemorrhoidal disease over time. These are blood loss, pain, prolapse, soiling and itching. These 5 items are graded using a 5-point Likert scale, ranging from (1) 'not at all', (2) 'a little', (3) 'reasonable', (4)'a lot' and (5) 'very much'. This results in a symptom score correlating with the severity of experienced HD symptoms. The PROM-HISS will be completed by e-mail. The PROM-HISS will assess a change of the symptoms over time. ThePROM-HISS is not validated yet, but an international validation study is being developed. Hence, the scale ranges are not clear yet.


Secondary Outcome Measures :
  1. Early complication(s) - Abscess [ Time Frame: This outcome measure will be assessed within 7 days post-procedure. ]
    Abscess will be assessed 7 days post-procedure. Abscess will be assessed by physical examination.

  2. Impact of symptoms on daily life and patient satisfaction with treatment [ Time Frame: 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. ]
    Assessed with the second part of the Patient-Reported Outcome Measure-Haemorrhoidal Impact and Satisfaction Score (PROM-HISS), which are each scored on a numeric rating scale from 0 to 10. Regarding impact of symptoms, 0 correlates with 'no impact at all' and 10 with 'highly impacted on daily life'. For patient satisfaction with treatment, this ranges between 0 'not satisfied' and 10 'very satisfied'. The PROM-HISS is not validated yet, but an international validation study is being developed. Hence, the scale ranges are not clear yet.

  3. Health Related Quality of Life [ Time Frame: 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. ]
    Measured by the EQ-5D-5L questionnaire and EQ-Visual Analogue Scale. These index scores are combined with length of life to calculate the QALY.

  4. Early complication(s) - Urinary retention [ Time Frame: This outcome measure will be assessed within 7 days post-procedure. ]
    Urinary retention will be assessed 7 days post-procedure. It will be assessed by ultrasonography.

  5. Late complication(s) - Incontinence [ Time Frame: Incontinence will be assessed at 52 weeks (1 year) post-procedure. ]
    The Wexner Fecal Incontinence Score will be used to assess incontinence.

  6. Late complication(s) - Anal stenosis [ Time Frame: Anal stenosis will be assessed at 52 weeks (1 year) post-procedure. ]
    Anal stenosis will be assessed by physical examination.

  7. Late complication(s) - Fistula [ Time Frame: Fistula will be assessed at 52 weeks (1 year) post-procedure. ]
    Fistula will be assessed by physical examination, in case this is inconclusive, MR imaging will be performed.

  8. Costs [ Time Frame: The questionnaires will be filled out at baseline, 6 weeks and 12 months follow-up. ]
    Total costs over the course of 12 months will be calculated by multiplying resource use with the costs per unit. Resource use(e.g. treatment, control visits, visits to the GP, other diagnostic/medical procedures, medication) will be obtained from the CRFand from recall cost-questionnaires (e.g. over the-counter medication, and lost work days). Sources for valuation of the costs will be cost prices of the Dutch costing manual and cost prices from thePharmaco therapeutic compass. If necessary, local hospital cost prices or otherwise NZa tariffs will be used, which are largely based on integral cost prices from the Dutch hospitals. Absence of work will be calculated by using the friction cost method,which is recommended by the Dutch manual for costing (Zorginstituut Nederland, 2015).

  9. Cost-effectiveness [ Time Frame: The EQ-5D-5L will be administered at baseline, 1 week, 6 weeks and at 12 months follow-up. ]
    The cost-effectiveness analysis from the healthcare perspective will be based on the cumulative proportion of patients whopresent with a recurrence up to 12 months follow-up. The cost-effectiveness analysis from the societal perspective (QALYs as outcome) will be based on the EQ-5D-5L.

  10. Budget Impact Analysis [ Time Frame: Time horizon of 5 years. ]
    A budget impact analysis (BIA) will be performed in accordance with the Dutch guidelines for economic evaluations and the ISPOR guidelines. The BIA will be performed from different perspectives (e.g. societal, healthcare) with a time horizon of 5 years. As input for the BIA, we will use the results that will become available from the clinical and cost-effectiveness study.The BIA will be performed using a simple decision analytic model. Different scenarios will be compared to investigate various levels of implementation or full substitution of any of the 3 interventions, as well as the swiftness of implementation (1-5 years). In order to test the robustness of the results, sensitivity analyses will be performed on data input and assumptions. No discounting will be performed. The target population in the BIA will be similar to the study population.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04101773


Contacts
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Contact: Sara Kuiper, MD +31(0)626731279 s.kuiper@maastrichtuniversity.nl

Locations
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Netherlands
Maastricht University Medical Centre
Maastricht, Limburg, Netherlands, 6229HX
Contact: Sara Kuiper, MD    +31(0)626731279    s.kuiper@maastrichtuniversity.nl   
Contact: Stephanie Breukink, MD PhD    +31(0)43-3872807    s.breukink@mumc.nl   
Principal Investigator: Sara Kuiper, MD         
Ziekenhuisgroep Twente
Almelo, Netherlands
Contact: Lutke Holzink         
Meander Medisch Centrum
Amersfoort, Netherlands
Contact: Consten         
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands
Contact: DeCastro         
Gelre Ziekenhuizen
Apeldoorn, Netherlands
Contact: Duijvendijk         
Rijnstate Ziekenhuis
Arnhem, Netherlands
Contact: Vening         
IJsselland Ziekenhuis
Capelle Aan Den IJssel, Netherlands
Contact: Doornebosch         
Reinier de Graaf Gasthuis
Delft, Netherlands
Contact: Dekker         
Groene Hart Ziekenhuis
Gouda, Netherlands
Contact: Baeten         
Elkerliek Ziekenhuis
Helmond, Netherlands
Contact: Schipper         
Medisch Centrum Leeuwarden
Leeuwarden, Netherlands
Contact: Koopal         
Canisius Wilhelmina Ziekenhuis
Nijmegen, Netherlands
Contact: Hansson         
Laurentius Ziekenhuis
Roermond, Netherlands
Contact: Heemskerk         
Diakonessenhuis
Utrecht, Netherlands
Contact: Pronk         
Máxima Medisch Centrum
Veldhoven, Netherlands
Contact: Dielen         
VieCurie Medisch Centrum
Venlo, Netherlands
Contact: Vogelaar         
Sponsors and Collaborators
Maastricht University Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
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Study Chair: Stephanie Breukink, MD PhD Maastricht University Medical Centre

Additional Information:
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Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT04101773    
Other Study ID Numbers: 852002023
First Posted: September 24, 2019    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Not yet discussed with research group.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Maastricht University Medical Center:
hemorrhoids
haemorrhoidal disease
recurrence
rubber band ligation
haemorrhoidectomy
Additional relevant MeSH terms:
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Hemorrhoids
Rectal Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Vascular Diseases
Cardiovascular Diseases