Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging

Study Overview
=================
Brief Summary
-----------------
Aortic aneurysms represent the most common and dangerous aortic diseases. Although conventional aortic repair techniques cure the disease, there is a high risk of paraplegia particularly in extensive thoracoabdominal aneurysms due to impaired blood supply to the spinal cord. The PAPA-ARTiS trial will assess the clinical safety and efficacy of the MISACE (Minimally-Invasive Segmental Artery Coil-Embolization) procedure, a novel therapeutic concept to reduce the risk of paraplegia due to aneurysm repair. The study investigates the MISACE procedure as a potential pre-treatment prior to open or endovascular aneurysm repair in patients with thoracoabdominal aortic aneurysms. Patients will be randomized to one of the two treatment strategies: a) aneurysm repair without MISACE pre-treatment, or b) aneurysm repair with MISACE pre-treatment.

Detailed Description
-----------------
Chronic aortic aneurysms are permanent and localized dilations of the aorta that remain asymptomatic for long periods of time, but continue to increase in diameter before they eventually rupture. Left untreated, the patients' prognosis is dismal, since the internal bleeding of the rupture brings about sudden death. Although successful treatment cures the disease, the risky procedures compromise spinal cord blood supply acutely and permanently, frequently leading to paraplegia, particularly for aneurysms involving crucial segmental arteries, i.e. thoracoabdominal aortic aneurysms of Crawford type II & III. Although various strategies have achieved a remarkable decrease in the incidence of paraplegia, it is still no less than 10-20%. However, it has recently been found that the deliberate staged occlusion of the segmental arteries to the paraspinous collateral network finally supplying the spinal cord can trigger arterial collateralization, thus stabilizing blood supply from alternate inflow sources and preventing ischaemia. This has been translated to a clinically available therapeutic option, 'minimally invasive staged segmental artery coil embolization' (MISACE), which proceeds in a 'staged' manner to occlude groups of arteries under highly controlled conditions, after which time must be allowed for arteriogenesis to build a robust collateral blood supply. PAPA-ARTiS is a multi-national, prospective, open-label, two-arm, randomized controlled trial to demonstrate, that a minimally invasive staged treatment approach can reduce paraplegia and mortality in patients undergoing thoracoabdominal aortic aneurysm (TAAA) repair. Patients with planned aneurysm repair will be included in the study and will be randomized 1:1 in the control group or the MISACE-group. The control group receives treatment as per standard institutional protocol - open or endovascular repair without MISACE. In the MISACE-group, segmental arteries will be occluded in one to three sessions some weeks before the definite repair. Segmental arteries are occluded with coils or plugs.This induces arteriogenesis and the building of a robust collateral network ultimately supplying the spinal cord. During aneurysm repair, these new arteries provide an alternate blood supply to the spinal cord and thereby help prevent paraplegia.

Official Title
-----------------
Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging With 'Minimally-Invasive Segmental Artery Coil-Embolization': A Randomized Controlled Multicentre Trial - PAPAartis

Conditions
-----------------
Aortic Aneurysm, Thoracoabdominal

Intervention / Treatment
-----------------
* Procedure: Minimally-Invasive Segmental Artery Coil-Embolization


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: TAAA, Crawford type II or III planned open or endovascular repair of aneurysm within four months ≥ 18 years old Exclusion Criteria: complicated (sub-) acute type B aortic dissection ruptured and urgent aneurysm (emergencies) untreated aortic arch aneurysm bilaterally occluded iliac arteries or chronic total occlusion of left subclavian artery pre-operative neurological deficits or spinal cord dysfunction major untreated cardio-pulmonary disease life-expectancy of less than one year high risk for segmental artery embolism severe contrast agent allergy, severe reduction in glomerular filtration rate (CKD stage 4) expected lack of compliance pregnant or nursing women impaired thyroid function, if not under stable treatment women of child bearing potential without highly effective contraceptive measures current participation in other interventional clinical trial patients under legal supervision or guardianship patients placed in an institution by official or court order

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MISACE arm<br>Minimally-Invasive Segmental Artery Coil-Embolization MISACE procedure prior to aneurysm repair segmental arteries are occluded with coils or plugs in one to three MISACE sessions (staged procedure) | Procedure: Minimally-Invasive Segmental Artery Coil-Embolization<br>* During one single MISACE session 3-7 segmental arteries will be occluded. The procedure is conducted through a peripheral artery access in local anaesthesia. Microcoils or vascular plugs will be used for the occlusion itself.<br>|
| No Intervention: control arm<br>receives treatment of aneurysm as usual: open surgical repair or endovascular repair without MISACE | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective is to greatly reduce incidence of ischaemic spinal cord injury and mortality. | Successful treatment of the aneurysm is a binary variable. All of the following criteria must be met for this composite endpoint to count as a success: The patient is alive and without substantial spinal cord injury 30 days after treatment, and the aneurysm did not rupture and has been excluded within six months of randomization. Substantial spinal cord injury will be determined with a modified Tarlov scale (see below). | 30 days after TAAA repair | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| substantial spinal cord injury | Substantial spinal cord injury is defined as zero to two on the modified Tarlov scale. 0. No lower extremity movement Lower extremity motion without gravity Lower extremity motion against gravity Able to stand with assistance Able to walk with assistance Normal | 30 days after TAAA repair and at one year after TAAA repair | 
| spinal cord injury according to the modified Tarlov scale from TAAA repair to one year | Spinal cord injury will be determined with a modified Tarlov scale (see above). | from date of TAAA repair and up to one year after TAAA repair | 
| mortality | all-cause mortality | at 30 days and one year after TAAA repair | 
| stay in intensive care unit and intermediate care | length of stay in intensive care unit and intermediate care unit after TAAA repair | from date of TAAA repair and up to one year after TAAA repair | 
| sub-group analyses | sub-group analyses of spinal cord injury according to modified Tarlov scale (see above) for open repair and endovascular repair separately | up to one year after TAAA repair | 
| sub-group analyses | sub-group analyses of mortality for open repair and endovascular repair separately | up to one year after TAAA repair | 
| re-operation for bleeding | re-operation for bleeding (only for open repair) | from date of TAAA repair and up to one year after TAAA repair | 
| cross-clamping times | cross-clamping times during open surgery | during open surgery | 
| residual aneurysm sac perfusion | residual aneurysm sac perfusion, i.e. type II endoleaks (only for endovascular repair) | up to one year after TAAA repair | 
| costs | incremental cost-effectiveness ratio (ICER) will be calculated | up to one year after TAAA repair | 
| Quality Adjusted Life Years | Quality Adjusted Life Years (QALYs) will be estimated over one year | up to one year after TAAA repair | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Paraplegia, Aortic Aneurysm Repair, Staging, Embolization, TAAA, Thoracoabdominal aortic aneurysm, MISACE, Spinal cord ischemia, Spinal cord ischaemia, Spinal cord injury, Spinal cord ischemic injury, Spinal cord ischaemic injury, Permanent paraplegia, Temporary paraplegia, Paraparesis, SCI, TAAA repair, Open TAAA repair, Open surgical TAAA repair, Endovascular TAAA repair, TEVAR, Aortic surgery, Thoracoabdominal aortic surgery, Type B aortic dissection, Chronic type B aortic dissection, Stanford type B aortic dissection, Collateral network, Paraspinal collateral network, Paraspinous collateral network, Arteriogenesis, Intercostal arteries