Coeliac Artery Release or Sham Operation (CARoSO)

March 11, 2024 updated by: R. H. Geelkerken, Medisch Spectrum Twente

Coeliac Artery Release or Sham Operation in Patients Suspected of the Median Arcuate Ligament Syndrome

In patients with Median Arcuate Ligament Syndrome (MALS), significant external compression of the coeliac artery (CA) by the median arcuate ligament (MAL) increasing mucosal ischemia (1,2) is assumed to cause chronic disabling postprandial abdominal pain, weight loss, and consequently lethargy and social deprivation (3,8). The majority of these patients have had a long medical journey before the diagnosis MALS is considered resulting in a substantial burden of disease and high healthcare and societal costs.

Although a Systematic Review have shown a sustainable symptom relief of 68% and a significant and durable improvement of quality of life after surgical treatment for MALS (4), there is still no (inter)national consensus on the existence and treatment of MALS (1, 5, 6, 7).

Two recent guidelines (3, 8) concluded that patients with MALS might be considered for surgical CA release (Recommendation 25 GRADE 2D; expert agreement 96%, Terlouw 2020). To end the ongoing debate and to enable the development of evidence-based guidelines for the management of MALS, both guideline committees recommend to perform a blinded, randomised controlled trial comparing a CA release with a sham operation. The proposed Coeliac Artery Release or Sham Operation study will either underline the usefulness of eCAR as a minimal invasive (cost)effective treatment for MALS or it will prohibit a meaningless intervention in patients with disabling abdominal symptoms.

If the CARoSO study proves that the treatment of MALS by eCAR is effective, to 490 patients with chronic disabling abdominal symptoms per year can be treated in the Netherlands. Effective treatment of MALS is expected to result in mean health gain of 6.05 Quality Adjusted Life Years (QALYs)/patient and has the potency to reduce the substantial productivity loss and healthcare consumption caused by MALS, resulting in a saving up to M€4.3/year. The outcome of the CARoSO study will be translated into strong recommendations in the coming updates of the relevant (inter)national multidisciplinary guidelines and will be adapted in daily practice.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The involved professions and the patient representatives unanimously recommend as primary endpoint for this study the proposed disease specific outcome measure: symptom relief measured on a VAS and PGI-I scale. This clinical outcome parameter can be reliable assessed within 6 months after the CA release (1, 9, 10). A two years follow up is suggested to extinguish the positive effect of attention in the diagnostic phase (11).

This study design allows for patient and observer blinding and for the sham group the eCAR approach is still feasible if the CARoSO outcome support this without applying additional scar tissue. A sham operation without skin incisions results in unblinding for the patient and the observer and thus undermines the basis of the evidential value of this study. There are no known cases where irreversible damage such as the intestinal infarction has occurred due to not treating this condition. Possible risks of not treating are continuous (pain) complaints and weight loss. The patients who undergo the sham operation and who still have complaints after unblinding of the study and proven effectivity of eCAR can still undergo the endoscopic AC release.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Floor FM Metz, MD
  • Phone Number: +31 534872000
  • Email: caroso@mst.nl

Study Locations

  • Netherlands
    • Overijssel
      • Enschede, Overijssel, Netherlands
        • Recruiting
        • Medisch Spectrum Twente
        • Contact:
          • Bob Geelkerken, Prof

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with a consensus diagnosis of MALS based on a multidisciplinary discussion in the two Dutch expert centers for Mesenteric Ischemia (Medisch Spectrum Twente and Erasmus Medical Centre). The multidisciplinary team contains of a vascular surgeon, gastroenterologist, radiologist as recommended in the guidelines.
  • Typical complaints: post-prandial pain and at least two of the following: dietary modification, unexplained weight loss, unexplained diarrhea.
  • Eccentric stenosis of ≥70% of the AC at the medial arcuatum ligament, demonstrated by two imaging techniques (duplex, MRA, CTA or DSA), including at least an inspiration and expiration CTA with 1mm sections. (Definition percent stenosis according to ECST 1998 formula: % stenosis = (1 - [diameter at the site of stenosis/estimated original diameter at the site of the stenosis]) x 100).
  • Ultrasound Abdomen without other more common abnormalities.
  • Gastroscopy-duodenoscopy without abnormalities, unless appropriate for mucosal ischemia.

Exclusion Criteria:

  • Patient not suitable for endoscopic AC release (e.g. previous surgery in the operating area).
  • Pregnancy.
  • Previous (endovascular) intervention of the visceral arteries.
  • A significant stenosis in the superior or in the inferior mesenteric artery.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: endoscopic Coeliac Artery Release (eCAR)
Patients randomized in the Intervention Group.
Procedure: Endoscopic Coeliac Artery Release (eCAR)
Endoscopic Coeliac Artery Release (eCAR); The Median Arcuate Ligament will be cleaved via an endoscopic retroperitoneal approach using a 4 trocar technique described in detail by van Petersen (12). To rule out learning curves and procedural variation all the procedures will be performed by two experienced eCAR surgeons in the MST-Dutch Expert Centre of Gastrointestinal Ischemia. All procedures will be videotaped. Both eCAR surgeons will not be involved in the follow up procedures.
Sham Comparator: Sham Operation
Patients randomized in the Sham group.
Procedure: Sham Operation
The sham operation consists of making 4 incisions up to the fascia similar to endoscopic AC release (eCAR). After 60 to 75 minutes of general anesthesia, in accordance with the average operating time of eCAR, the sham operation is ended. This study design allows for patient and observer blinding and for the sham group the eCAR approach is still feasible if the CARoSO outcome support this without applying additional scar tissue.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of patients with significant reduction in abdominal symptoms on a VAS scale
Time Frame: 6 months after randomization

The change in abdominal symptoms is measured with a composite primary end point (CPE) at 6 months after randomization existing of o the daily visual analogue scale (VAS) for abdominal pain

  • every day for seven days, the patients is asked to indicate the average abdominal pain of the past 24 hours on a VAS, this calculates the average VAS for that week.
  • The PGI-I consists of one question about the change in symptoms compared to before surgery indicated on a 7-point Likert scale with the possible answers: "very much improved", "greatly improved", "somewhat improved", " no change", "slightly deteriorated", "greatly deteriorated" and "very much worse". - A significant reduction in abdominal symptoms at 6 months after randomization is defined as an o a reduction in mean abdominal pain VAS (0-100) of ≥50% compared to baseline
6 months after randomization
The number of patients with significant reduction in abdominal symptoms.
Time Frame: 6 months after randomization
The change in abdominal symptoms is measured with a composite primary end point (CPE) at 6 months after randomization o "much improved" or "very much improved" symptoms on the PGI-I (12) (7-point Likert Scale). The PGI-I consists of one question about the change in symptoms compared to before surgery.
6 months after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Abdominal pain measured with mean abdominal pain VAS endpoint)
Time Frame: Preoperative and 3, 6, 12 and 18 months after operation
Visual Analogue Scale from 0-100
Preoperative and 3, 6, 12 and 18 months after operation
Change in complaints measured with the PGI-I
Time Frame: 3, 6, 12 and 18 months after operation
PGI-I on a 7-point Likert Scale
3, 6, 12 and 18 months after operation
Abdominal pain measured with worst abdominal pain VAS
Time Frame: Preoperative and 3, 6, 12, 18 and 24 months after operation
Preoperative and 3, 6, 12, 18 and 24 months after operation
HR-QoL measured with the EQ-5D-5L
Time Frame: Preoperative and 3, 6, 12, 18 and 24 months after operation
Visual Analogue Scale from 0-100
Preoperative and 3, 6, 12, 18 and 24 months after operation
HR-QoL measured with the SF-12
Time Frame: Preoperative and 3, 6, 12, 18 and 24 months after operation
SF-12 from 0-100
Preoperative and 3, 6, 12, 18 and 24 months after operation
Productivity loss measured with the iPCQ (Productivity Costs Questionnaire)
Time Frame: 3, 6 and 24 months after randomization
Measured in euro per patient
3, 6 and 24 months after randomization
Healthcare consumption measured with the iMCQ
Time Frame: 3, 6 and 24 months after operation
Measured in euro per patient
3, 6 and 24 months after operation
Cost-utility ratio (ICUR) of AC release compared to a sham operation
Time Frame: 3, 6 and 24 months after operation
Cost per additional QALY in 6 months
3, 6 and 24 months after operation
The number of anatomically successful procedures, defined as ≤30% stenosis (diameter permeated lumen/diameter artery*100) measured with a CTa/MRa
Time Frame: 6 months after operation
Amount of anatomically succesful procedures
6 months after operation
The number of days until return to a normal diet
Time Frame: 24 months after operation
24 months after operation
Weight
Time Frame: Preoperative and 3, 6, 12 and 18 months after operation
Kilograms
Preoperative and 3, 6, 12 and 18 months after operation
Success of blinding
Time Frame: 3, 6, 12, 18 and 24months after operation
By asking the patient in which treatment group they were randomzied
3, 6, 12, 18 and 24months after operation
Complications classified in the Clavien-Dindo classification
Time Frame: 30 days after operation
Questionnaire
30 days after operation
Percentage of patients undergoing additional PTA or other surgical treatment
Time Frame: 24 months after operation
Percentage of patients
24 months after operation
QoL measured by WHO-QoL Bref
Time Frame: Preoperative and 3, 6, 12, 18 and 24 months after operation
Scale 0-100
Preoperative and 3, 6, 12, 18 and 24 months after operation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medisch Spectrum Twente

Collaborators

Medical School Medisch Spectrum Twente
Techmed University of Twente
Erasmus Medical Centre

Investigators

  • Principal Investigator: RH Geelkerken, MD PHD, Medisch Spectrum Twente

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2022

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

July 14, 2022

First Submitted That Met QC Criteria

July 18, 2022

First Posted (Actual)

July 21, 2022

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 11, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • X

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Mesenteric Ischemia

Clinical Trials on Endoscopic Coeliac Artery Release (eCAR)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Montenegro

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe