Clinical trial NCT03434314: Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging
Official title: Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging With 'Minimally-Invasive Segmental Artery Coil-Embolization': A Randomized Controlled Multicentre Trial - PAPAartis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Aneurysm, Thoracoabdominal
Keywords: 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
Lead sponsor: University of Leipzig
Sponsor class: OTHER
Collaborators: name: European Commission
name: German Research Foundation
name: Universidad de Granada
name: European Clinical Research Infrastructure Network
name: Modus Research and Innovation Limited
name: Rigshospitalet, Denmark
name: European Society of Cardiology
name: Baylor College of Medicine
name: University of Pennsylvania
First posted: 2018-02-15
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The primary objective is to greatly reduce incidence of ischaemic spinal cord injury and mortality.
timeFrame: 30 days after TAAA repair
Secondary outcomes:
measure: substantial spinal cord injury
timeFrame: 30 days after TAAA repair and at one year after TAAA repair
measure: spinal cord injury according to the modified Tarlov scale from TAAA repair to one year
timeFrame: from date of TAAA repair and up to one year after TAAA repair
measure: mortality
timeFrame: at 30 days and one year after TAAA repair
measure: stay in intensive care unit and intermediate care
timeFrame: from date of TAAA repair and up to one year after TAAA repair
measure: sub-group analyses
timeFrame: up to one year after TAAA repair
measure: sub-group analyses
timeFrame: up to one year after TAAA repair
measure: re-operation for bleeding
timeFrame: from date of TAAA repair and up to one year after TAAA repair
measure: cross-clamping times
timeFrame: during open surgery
measure: residual aneurysm sac perfusion
timeFrame: up to one year after TAAA repair
measure: costs
timeFrame: up to one year after TAAA repair
measure: Quality Adjusted Life Years
timeFrame: up to one year after TAAA repair
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Vienna
country: Austria
facility: Herzzentrum Hietzing
city: Bordeaux
country: France
facility: University Hospital of Bordeaux
city: Le Plessis-Robinson
country: France
facility: Marie Lannelongue Hospital
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Essen
country: Germany
facility: Westdeutsches Herz und Gefäßzentrum Essen
city: Freiburg
country: Germany
facility: Universitäts-Herzzentrum Freiburg/ Bad Krozingen
city: Hamburg
country: Germany
facility: Herzzentrum Hamburg
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
city: Leipzig
country: Germany
facility: UniversitätskIinikum Leipzig
city: Munich
country: Germany
facility: Klinikum rechts der Isar (TU München)
city: München
country: Germany
facility: Klinikum der Universität München (LMU)
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Nuremberg
country: Germany
facility: Paracelsus Universität - Klinikum Nürnberg
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Bologna
country: Italy
facility: S.Orsola-Malpighi Hospital
city: Milano
country: Italy
facility: Ospedale San Raffaele SRL
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Warsaw
country: Poland
facility: Medical University of Warsaw
city: Zabrze
country: Poland
facility: Silesian Center for Heart Diseases
city: Malmö
country: Sweden
facility: Lund University Hospital Malmoe
city: Örebro
country: Sweden
facility: Örebro University Hospital
city: Bern
country: Switzerland
facility: Bern University Hospital
city: London
country: United Kingdom
facility: St Bartholomews Hospital
Study officials:
affiliation: University Leipzig
name: Christian D Etz, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Petroff D, Czerny M, Kolbel T, Melissano G, Lonn L, Haunschild J, von Aspern K, Neuhaus P, Pelz J, Epstein DM, Romo-Aviles N, Piotrowski K, Etz CD. Paraplegia prevention in aortic aneurysm repair by thoracoabdominal staging with 'minimally invasive staged segmental artery coil embolisation' (MIS(2)ACE): trial protocol for a randomised controlled multicentre trial. BMJ Open. 2019 Mar 4;9(3):e025488. doi: 10.1136/bmjopen-2018-025488.