Coeliac Artery Release or Sham Operation

NCT05468580 | Recruiting DMC

• 1 other identifier: X
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mesenteric Ischemia; Median Arcuate Ligament Syndrome; Dunbar Syndrome; Coeliac Artery Compression; Celiac Artery Compression Syndrome

Keywords

MALS; Mesenteric ischaemia; Quality of Life; Coeliac Artery Release; Sham Operation; Healthcare Costs

Outcome Measures

Primary Outcomes (2)

• The number of patients with significant reduction in abdominal symptoms on a VAS scale

  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.

  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 Outcomes (15)

• Abdominal pain measured with mean abdominal pain VAS endpoint)

  Preoperative and 3, 6, 12 and 18 months after operation

• Change in complaints measured with the PGI-I

  3, 6, 12 and 18 months after operation

• Abdominal pain measured with worst abdominal pain VAS

  Preoperative and 3, 6, 12, 18 and 24 months after operation

• HR-QoL measured with the EQ-5D-5L

  Preoperative and 3, 6, 12, 18 and 24 months after operation

• HR-QoL measured with the SF-12

  Preoperative and 3, 6, 12, 18 and 24 months after operation

Study Arms (2)

endoscopic Coeliac Artery Release (eCAR)

ACTIVE COMPARATOR

Patients randomized in the Intervention Group.

Procedure: Endoscopic Coeliac Artery Release (eCAR)

Sham Operation

SHAM COMPARATOR

Patients randomized in the Sham group.

Procedure: Sham Operation

Interventions

Endoscopic Coeliac Artery Release (eCAR) PROCEDURE

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.

endoscopic Coeliac Artery Release (eCAR)

Sham Operation PROCEDURE

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.

Sham Operation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medisch Spectrum Twente: lead
• Medical School Medisch Spectrum Twente: collaborator
• Techmed University of Twente: collaborator
• Erasmus Medical Centre: collaborator

Study Sites (1)

Medisch Spectrum Twente

Enschede, Overijssel, Netherlands

RECRUITING

Related Publications (12)

• Mensink PB, van Petersen AS, Kolkman JJ, Otte JA, Huisman AB, Geelkerken RH. Gastric exercise tonometry: the key investigation in patients with suspected celiac artery compression syndrome. J Vasc Surg. 2006 Aug;44(2):277-81. doi: 10.1016/j.jvs.2006.03.038.

  PMID: 16890853 BACKGROUND

• Berge ST, Safi N, Medhus AW, Sundhagen JO, Hisdal J, Kazmi SSH. Perioperative Microcirculatory Changes Detected with Gastroscopy Assisted Laser Doppler Flowmetry and Visible Light Spectroscopy in Patients with Median Arcuate Ligament Syndrome. Vasc Health Risk Manag. 2020 Aug 10;16:331-341. doi: 10.2147/VHRM.S252192. eCollection 2020.

  PMID: 32982262 BACKGROUND

• Bjorck M, Koelemay M, Acosta S, Bastos Goncalves F, Kolbel T, Kolkman JJ, Lees T, Lefevre JH, Menyhei G, Oderich G, Esvs Guidelines Committee, Kolh P, de Borst GJ, Chakfe N, Debus S, Hinchliffe R, Kakkos S, Koncar I, Sanddal Lindholt J, Vega de Ceniga M, Vermassen F, Verzini F, Document Reviewers, Geelkerken B, Gloviczki P, Huber T, Naylor R. Editor's Choice - Management of the Diseases of Mesenteric Arteries and Veins: Clinical Practice Guidelines of the European Society of Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2017 Apr;53(4):460-510. doi: 10.1016/j.ejvs.2017.01.010. No abstract available.

  PMID: 28359440 BACKGROUND

• Metz FM, Blauw JTM, Brusse-Keizer M, Kolkman JJ, Bruno MJ, Geelkerken RH; Dutch Mesenteric Ischaemia Study Group. Systematic Review of the Efficacy of Treatment for Median Arcuate Ligament Syndrome. Eur J Vasc Endovasc Surg. 2022 Dec;64(6):720-732. doi: 10.1016/j.ejvs.2022.08.033. Epub 2022 Sep 6.

  PMID: 36075541 BACKGROUND

• Szilagyi DE, Rian RL, Elliott JP, Smith RF. The celiac artery compression syndrome: does it exist? Surgery. 1972 Dec;72(6):849-63. No abstract available.

  PMID: 5087274 BACKGROUND

• Geelkerken RH, van Bockel JH, de Roos WK, Hermans J. Coeliac artery compression syndrome: the effect of decompression. Br J Surg. 1990 Jul;77(7):807-9. doi: 10.1002/bjs.1800770728.

  PMID: 2383757 BACKGROUND

• van Dijk LJD, Moons LMG, van Noord D, Moelker A, Verhagen HJM, Bruno MJ, Rouwet EV. Persistent symptom relief after revascularization in patients with single-artery chronic mesenteric ischemia. J Vasc Surg. 2018 Sep;68(3):779-785. doi: 10.1016/j.jvs.2017.12.038. Epub 2018 Mar 6.

  PMID: 29523436 BACKGROUND

• Terlouw LG, Moelker A, Abrahamsen J, Acosta S, Bakker OJ, Baumgartner I, Boyer L, Corcos O, van Dijk LJ, Duran M, Geelkerken RH, Illuminati G, Jackson RW, Karkkainen JM, Kolkman JJ, Lonn L, Mazzei MA, Nuzzo A, Pecoraro F, Raupach J, Verhagen HJ, Zech CJ, van Noord D, Bruno MJ. European guidelines on chronic mesenteric ischaemia - joint United European Gastroenterology, European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Gastrointestinal and Abdominal Radiology, Netherlands Association of Hepatogastroenterologists, Hellenic Society of Gastroenterology, Cardiovascular and Interventional Radiological Society of Europe, and Dutch Mesenteric Ischemia Study group clinical guidelines on the diagnosis and treatment of patients with chronic mesenteric ischaemia. United European Gastroenterol J. 2020 May;8(4):371-395. doi: 10.1177/2050640620916681. Epub 2020 Apr 16.

  PMID: 32297566 BACKGROUND

• Blauw JTM, Pastoors HAM, Brusse-Keizer M, Beuk RJ, Kolkman JJ, Geelkerken RH, For The Dutch Mesenteric Ischemia Study Group. The Impact of Revascularisation on Quality of Life in Chronic Mesenteric Ischemia. Can J Gastroenterol Hepatol. 2019 Nov 12;2019:7346013. doi: 10.1155/2019/7346013. eCollection 2019.

  PMID: 31781520 BACKGROUND

• Metz F, Blauw J, Brusse-Keizer M, Kolkman J, Geelkerken R. Quality of life temporarily improved in patients in whom the diagnosis chronic mesenteric ischemia wasn't confirmed after multidisciplinary evaluation in a tertiary referral centre. Japanese J Gastroenterol Res. 2022;2:1-6.

  BACKGROUND

• van Petersen AS, Vriens BH, Huisman AB, Kolkman JJ, Geelkerken RH. Retroperitoneal endoscopic release in the management of celiac artery compression syndrome. J Vasc Surg. 2009 Jul;50(1):140-7. doi: 10.1016/j.jvs.2008.12.077.

  PMID: 19563962 BACKGROUND

• Yalcin I, Bump RC. Validation of two global impression questionnaires for incontinence. Am J Obstet Gynecol. 2003 Jul;189(1):98-101. doi: 10.1067/mob.2003.379.

  PMID: 12861145 BACKGROUND

MeSH Terms

Conditions

Mesenteric Ischemia; Median Arcuate Ligament Syndrome

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Peritoneal Diseases; Vascular Diseases; Cardiovascular Diseases; Digestive System Abnormalities; Vascular Malformations; Cardiovascular Abnormalities; Arterial Occlusive Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• RH Geelkerken, MD PHD

  Medisch Spectrum Twente

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Floor FM Metz, MD

CONTACT

+31 534872000; caroso@mst.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients are randomized in a 1:1 fashion (stratified on preoperative abdominal pain VAS, psychiatric comorbidities and gender) for either endoscopic Coeliac Artery Release (eCAR) or a sham operation.The randomization takes place in the operating room by a randomization program. Except for the surgical team, all care providers are blinded. To maintain the blinding, there will be no (substantive) contact between the members of the operating team and the patient postoperatively (or in follow up). In the event of an emergency in a patient included in the CARoSO study envelopes will be 24/7 available to break the blind. Furthermore the study will be unblinded when the difference in effectiveness as described in the hypothesis is achieved for the primary outcome after the analyses on the 6 months outcomes (both primary and secondary) have been completed for all included subjects. This decision will be made by the Data Safety and Monotoring Board.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A nationwide randomized placebo-controlled patient and observer blinded clinical superiority trial.

Study Record Dates

• First Submitted: July 14, 2022
• First Posted: July 21, 2022
• Study Start: April 1, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

NL (1)