Coeliac Artery Release or Sham Operation in Patients Suspected of the Median Arcuate Ligament Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- The number of patients with significant reduction in abdominal symptoms.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
endoscopic Coeliac Artery Release (eCAR)
Patients randomized in the Intervention Group.
干预措施: Endoscopic Coeliac Artery Release (eCAR) (Procedure)
Sham Operation
Patients randomized in the Sham group.
干预措施: Sham Operation (Procedure)
结局指标
主要结局
The number of patients with significant reduction in abdominal symptoms.
时间窗: 6 months after randomization
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.
The number of patients with significant reduction in abdominal symptoms on a VAS scale
时间窗: 6 months after randomization
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
次要结局
- Abdominal pain measured with mean abdominal pain VAS endpoint)(Preoperative and 3, 6, 12 and 18 months after operation)
- Healthcare consumption measured with the iMCQ(3, 6 and 24 months after operation)
- HR-QoL measured with the EQ-5D-5L(Preoperative and 3, 6, 12, 18 and 24 months after operation)
- Success of blinding(3, 6, 12, 18 and 24months after operation)
- Complications classified in the Clavien-Dindo classification(30 days after operation)
- Change in complaints measured with the PGI-I(3, 6, 12 and 18 months after operation)
- HR-QoL measured with the SF-12(Preoperative and 3, 6, 12, 18 and 24 months after operation)
- Weight(Preoperative and 3, 6, 12 and 18 months after operation)
- QoL measured by WHO-QoL Bref(Preoperative and 3, 6, 12, 18 and 24 months after operation)
- Productivity loss measured with the iPCQ (Productivity Costs Questionnaire)(3, 6 and 24 months after randomization)
- The number of anatomically successful procedures, defined as ≤30% stenosis (diameter permeated lumen/diameter artery*100) measured with a CTa/MRa(6 months after operation)
- The number of days until return to a normal diet(24 months after operation)
- Percentage of patients undergoing additional PTA or other surgical treatment(24 months after operation)
- Abdominal pain measured with worst abdominal pain VAS(Preoperative and 3, 6, 12, 18 and 24 months after operation)
- Cost-utility ratio (ICUR) of AC release compared to a sham operation(3, 6 and 24 months after operation)
研究者
R. H. Geelkerken
Principal Investigator
Medisch Spectrum Twente