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
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
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 β€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
NCT ID
NCT05468580
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
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 Mβ¬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 β€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
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Results Reference
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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
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PubMed Identifier
28359440
Citation
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Results Reference
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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.
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Citation
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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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Citation
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Coeliac Artery Release or Sham Operation
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