MedPath

Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging

Not Applicable
Active, not recruiting
Conditions
Aortic Aneurysm, Thoracoabdominal
Interventions
Procedure: Minimally-Invasive Segmental Artery Coil-Embolization
Registration Number
NCT03434314
Lead Sponsor
University of Leipzig
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
500
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MISACE armMinimally-Invasive Segmental Artery Coil-EmbolizationMinimally-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)
Primary Outcome Measures
NameTimeMethod
The primary objective is to greatly reduce incidence of ischaemic spinal cord injury and mortality.30 days after TAAA repair

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).

Secondary Outcome Measures
NameTimeMethod
Quality Adjusted Life Yearsup to one year after TAAA repair

Quality Adjusted Life Years (QALYs) will be estimated over one year

spinal cord injury according to the modified Tarlov scale from TAAA repair to one yearfrom date of TAAA repair and up to one year after TAAA repair

Spinal cord injury will be determined with a modified Tarlov scale (see above).

mortalityat 30 days and one year after TAAA repair

all-cause mortality

sub-group analysesup to one year after TAAA repair

sub-group analyses of mortality for open repair and endovascular repair separately

re-operation for bleedingfrom date of TAAA repair and up to one year after TAAA repair

re-operation for bleeding (only for open repair)

substantial spinal cord injury30 days after TAAA repair and at one year after TAAA repair

Substantial spinal cord injury is defined as zero to two on the modified Tarlov scale.

0. No lower extremity movement

1. Lower extremity motion without gravity

2. Lower extremity motion against gravity

3. Able to stand with assistance

4. Able to walk with assistance

5. Normal

stay in intensive care unit and intermediate carefrom date of TAAA repair and up to one year after TAAA repair

length of stay in intensive care unit and intermediate care unit after TAAA repair

cross-clamping timesduring open surgery

cross-clamping times during open surgery

residual aneurysm sac perfusionup to one year after TAAA repair

residual aneurysm sac perfusion, i.e. type II endoleaks (only for endovascular repair)

costsup to one year after TAAA repair

incremental cost-effectiveness ratio (ICER) will be calculated

Trial Locations

Locations (29)

Marie Lannelongue Hospital

🇫🇷

Le Plessis-Robinson, France

Uniklinik RWTH Aachen

🇩🇪

Aachen, Germany

Herzzentrum Hietzing

🇦🇹

Vienna, Austria

University Hospital of Bordeaux

🇫🇷

Bordeaux, France

Universitätsklinikum Münster

🇩🇪

Münster, Germany

Universitätsklinikum Tübingen

🇩🇪

Tübingen, Germany

Universitätsklinikum Düsseldorf

🇩🇪

Düsseldorf, Germany

Herzzentrum Hamburg

🇩🇪

Hamburg, Germany

Westdeutsches Herz und Gefäßzentrum Essen

🇩🇪

Essen, Germany

Ospedale San Raffaele SRL

🇮🇹

Milano, Italy

Silesian Center for Heart Diseases

🇵🇱

Zabrze, Poland

Universitätsklinikum Regensburg

🇩🇪

Regensburg, Germany

Paracelsus Universität - Klinikum Nürnberg

🇩🇪

Nuremberg, Germany

Universitätsklinikum Heidelberg

🇩🇪

Heidelberg, Germany

S.Orsola-Malpighi Hospital

🇮🇹

Bologna, Italy

Maastricht University Medical Center

🇳🇱

Maastricht, Netherlands

Medical University of Warsaw

🇵🇱

Warsaw, Poland

Lund University Hospital Malmoe

🇸🇪

Malmö, Sweden

Bern University Hospital

🇨🇭

Bern, Switzerland

Örebro University Hospital

🇸🇪

Örebro, Sweden

St Bartholomews Hospital

🇬🇧

London, United Kingdom

Universitäts-Herzzentrum Freiburg/ Bad Krozingen

🇩🇪

Freiburg, Germany

Herzzentrum Leipzig

🇩🇪

Leipzig, Germany

UniversitätskIinikum Leipzig

🇩🇪

Leipzig, Germany

Klinikum rechts der Isar (TU München)

🇩🇪

Munich, Germany

Klinikum der Universität München (LMU)

🇩🇪

München, Germany

Deutsches Herzzentrum Berlin

🇩🇪

Berlin, Germany

Medizinische Hochschule Hannover

🇩🇪

Hanover, Germany

Medizinische Universität Innsbruck

🇦🇹

Innsbruck, Austria

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