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Coeliac Artery Release or Sham Operation (CARoSO)

Primary Purpose

Mesenteric Ischemia, Median Arcuate Ligament Syndrome, Dunbar Syndrome

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Endoscopic Coeliac Artery Release (eCAR)
Sham Operation
Sponsored by
Medisch Spectrum Twente
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mesenteric Ischemia focused on measuring MALS, Mesenteric ischaemia, Quality of Life, Coeliac Artery Release, Sham Operation, Healthcare Costs

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 β‰₯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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Sham Comparator

    Arm Label

    endoscopic Coeliac Artery Release (eCAR)

    Sham Operation

    Arm Description

    Patients randomized in the Intervention Group.

    Patients randomized in the Sham group.

    Outcomes

    Primary Outcome Measures

    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 β‰₯50% compared to baseline
    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.

    Secondary Outcome Measures

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

    Full Information

    First Posted
    July 14, 2022
    Last Updated
    July 18, 2022
    Sponsor
    Medisch Spectrum Twente
    Collaborators
    Medical School Medisch Spectrum Twente, Techmed University of Twente, Erasmus Medical Centre
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05468580
    Brief Title
    Coeliac Artery Release or Sham Operation
    Acronym
    CARoSO
    Official Title
    Coeliac Artery Release or Sham Operation in Patients Suspected of the Median Arcuate Ligament Syndrome
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2022 (Anticipated)
    Primary Completion Date
    October 1, 2026 (Anticipated)
    Study Completion Date
    June 1, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Medisch Spectrum Twente
    Collaborators
    Medical School Medisch Spectrum Twente, Techmed University of Twente, Erasmus Medical Centre

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    A nationwide randomized placebo-controlled patient and observer blinded clinical superiority trial.
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Masking Description
    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.
    Allocation
    Randomized
    Enrollment
    70 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    endoscopic Coeliac Artery Release (eCAR)
    Arm Type
    Active Comparator
    Arm Description
    Patients randomized in the Intervention Group.
    Arm Title
    Sham Operation
    Arm Type
    Sham Comparator
    Arm Description
    Patients randomized in the Sham group.
    Intervention Type
    Procedure
    Intervention Name(s)
    Endoscopic Coeliac Artery Release (eCAR)
    Intervention Description
    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.
    Intervention Type
    Procedure
    Intervention Name(s)
    Sham Operation
    Intervention Description
    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 Measure Information:
    Title
    The number of patients with significant reduction in abdominal symptoms on a VAS scale
    Description
    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 β‰₯50% compared to baseline
    Time Frame
    6 months after randomization
    Title
    The number of patients with significant reduction in abdominal symptoms.
    Description
    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.
    Time Frame
    6 months after randomization
    Secondary Outcome Measure Information:
    Title
    Abdominal pain measured with mean abdominal pain VAS endpoint)
    Description
    Visual Analogue Scale from 0-100
    Time Frame
    Preoperative and 3, 6, 12 and 18 months after operation
    Title
    Change in complaints measured with the PGI-I
    Description
    PGI-I on a 7-point Likert Scale
    Time Frame
    3, 6, 12 and 18 months after operation
    Title
    Abdominal pain measured with worst abdominal pain VAS
    Time Frame
    Preoperative and 3, 6, 12, 18 and 24 months after operation
    Title
    HR-QoL measured with the EQ-5D-5L
    Description
    Visual Analogue Scale from 0-100
    Time Frame
    Preoperative and 3, 6, 12, 18 and 24 months after operation
    Title
    HR-QoL measured with the SF-12
    Description
    SF-12 from 0-100
    Time Frame
    Preoperative and 3, 6, 12, 18 and 24 months after operation
    Title
    Productivity loss measured with the iPCQ (Productivity Costs Questionnaire)
    Description
    Measured in euro per patient
    Time Frame
    3, 6 and 24 months after randomization
    Title
    Healthcare consumption measured with the iMCQ
    Description
    Measured in euro per patient
    Time Frame
    3, 6 and 24 months after operation
    Title
    Cost-utility ratio (ICUR) of AC release compared to a sham operation
    Description
    Cost per additional QALY in 6 months
    Time Frame
    3, 6 and 24 months after operation
    Title
    The number of anatomically successful procedures, defined as ≀30% stenosis (diameter permeated lumen/diameter artery*100) measured with a CTa/MRa
    Description
    Amount of anatomically succesful procedures
    Time Frame
    6 months after operation
    Title
    The number of days until return to a normal diet
    Time Frame
    24 months after operation
    Title
    Weight
    Description
    Kilograms
    Time Frame
    Preoperative and 3, 6, 12 and 18 months after operation
    Title
    Success of blinding
    Description
    By asking the patient in which treatment group they were randomzied
    Time Frame
    3, 6, 12, 18 and 24months after operation
    Title
    Complications classified in the Clavien-Dindo classification
    Description
    Questionnaire
    Time Frame
    30 days after operation
    Title
    Percentage of patients undergoing additional PTA or other surgical treatment
    Description
    Percentage of patients
    Time Frame
    24 months after operation
    Title
    QoL measured by WHO-QoL Bref
    Description
    Scale 0-100
    Time Frame
    Preoperative and 3, 6, 12, 18 and 24 months after operation

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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 β‰₯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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Floor FM Metz, MD
    Phone
    +31 534872000
    Email
    flores.metz@mst.nl
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    RH Geelkerken, MD PHD
    Organizational Affiliation
    Medisch Spectrum Twente
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    16890853
    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.
    Results Reference
    background
    PubMed Identifier
    32982262
    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.
    Results Reference
    background
    PubMed Identifier
    28359440
    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.
    Results Reference
    background
    PubMed Identifier
    36075541
    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.
    Results Reference
    background
    PubMed Identifier
    5087274
    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.
    Results Reference
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    PubMed Identifier
    2383757
    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.
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    PubMed Identifier
    29523436
    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.
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    PubMed Identifier
    32297566
    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.
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    PubMed Identifier
    31781520
    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.
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    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.
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    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.
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