Coeliac Artery Release or Sham Operation

Official title

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

Overview

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.

Interventions

• 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.
• 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.

Primary outcome measures

• The number of patients with significant reduction in abdominal symptoms on a VAS scale [Time frame: 6 months after randomization]
• The number of patients with significant reduction in abdominal symptoms. [Time frame: 6 months after randomization]

Secondary outcome measures (12)

• Abdominal pain measured with mean abdominal pain VAS endpoint) [Time frame: 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]
• Abdominal pain measured with worst abdominal pain VAS [Time frame: 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]
• HR-QoL measured with the SF-12 [Time frame: 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]
• Healthcare consumption measured with the iMCQ [Time frame: 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]
• 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]
• The number of days until return to a normal diet [Time frame: 24 months after operation]
• Weight [Time frame: Preoperative and 3, 6, 12 and 18 months after operation]
• Success of blinding [Time frame: 3, 6, 12, 18 and 24months after operation]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• Medisch Spectrum Twente — Enschede

Publications

• 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
• 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
• 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 Mesente PMID 28359440
• 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
• 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
• 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
• 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
• 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 Gas PMID 32297566

Identifiers

NCT: NCT05468580 · X

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗