Clinical trial NCT05468580: Coeliac Artery Release or Sham Operation
Official title: Coeliac Artery Release or Sham Operation in Patients Suspected of the Median Arcuate Ligament Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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
Lead sponsor: Medisch Spectrum Twente
Sponsor class: OTHER
Collaborators: name: Medical School Medisch Spectrum Twente
name: Techmed University of Twente
name: Erasmus Medical Centre
First posted: 2022-07-21
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A nationwide randomized placebo-controlled patient and observer blinded clinical superiority trial.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The number of patients with significant reduction in abdominal symptoms on a VAS scale
timeFrame: 6 months after randomization
measure: The number of patients with significant reduction in abdominal symptoms.
timeFrame: 6 months after randomization
Secondary outcomes:
measure: Abdominal pain measured with mean abdominal pain VAS endpoint)
timeFrame: Preoperative and 3, 6, 12 and 18 months after operation
measure: Change in complaints measured with the PGI-I
timeFrame: 3, 6, 12 and 18 months after operation
measure: Abdominal pain measured with worst abdominal pain VAS
timeFrame: Preoperative and 3, 6, 12, 18 and 24 months after operation
measure: HR-QoL measured with the EQ-5D-5L
timeFrame: Preoperative and 3, 6, 12, 18 and 24 months after operation
measure: HR-QoL measured with the SF-12
timeFrame: Preoperative and 3, 6, 12, 18 and 24 months after operation
measure: Productivity loss measured with the iPCQ (Productivity Costs Questionnaire)
timeFrame: 3, 6 and 24 months after randomization
measure: Healthcare consumption measured with the iMCQ
timeFrame: 3, 6 and 24 months after operation
measure: Cost-utility ratio (ICUR) of AC release compared to a sham operation
timeFrame: 3, 6 and 24 months after operation
measure: The number of anatomically successful procedures, defined as ≤30% stenosis (diameter permeated lumen/diameter artery*100) measured with a CTa/MRa
timeFrame: 6 months after operation
measure: The number of days until return to a normal diet
timeFrame: 24 months after operation
measure: Weight
timeFrame: Preoperative and 3, 6, 12 and 18 months after operation
measure: Success of blinding
timeFrame: 3, 6, 12, 18 and 24months after operation
measure: Complications classified in the Clavien-Dindo classification
timeFrame: 30 days after operation
measure: Percentage of patients undergoing additional PTA or other surgical treatment
timeFrame: 24 months after operation
measure: QoL measured by WHO-QoL Bref
timeFrame: Preoperative and 3, 6, 12, 18 and 24 months after operation
Other outcomes:
Locations:
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
state: Overijssel
Study officials:
affiliation: Medisch Spectrum Twente
name: RH Geelkerken, MD PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.