Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging (PAPAartis)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Aneurysm, Thoracoabdominal
• Intervention / Treatment: Procedure: Minimally-Invasive Segmental Artery Coil-Embolization

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.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christian D Etz, Prof. Dr.; Phone Number: +49 341 865 251007; Email: christian.etz@medizin.uni-leipzig.de
• Study Contact Backup: Name: David Petroff, Dr.; Phone Number: +49 341 97 16 354; Email: david.petroff@zks.uni-leipzig.de

Study Locations

• Austria
  • Innsbruck, Austria
    • Medizinische Universitat Innsbruck
  • Vienna, Austria
    • Herzzentrum Hietzing
• France
  • Bordeaux, France
    • University Hospital of Bordeaux
  • Le Plessis-Robinson, France
    • Marie Lannelongue Hospital
• Germany
  • Aachen, Germany
    • Uniklinik RWTH Aachen
  • Berlin, Germany
    • Deutsches Herzzentrum Berlin
  • Düsseldorf, Germany
    • Universitätsklinikum Düsseldorf
  • Essen, Germany
    • Westdeutsches Herz und Gefäßzentrum Essen
  • Freiburg, Germany
    • Universitäts-Herzzentrum Freiburg/ Bad Krozingen
  • Hamburg, Germany
    • Herzzentrum Hamburg
  • Hanover, Germany
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany
    • Universitätsklinikum Heidelberg
  • Leipzig, Germany
    • Herzzentrum Leipzig
  • Leipzig, Germany
    • UniversitätskIinikum Leipzig
  • Munich, Germany
    • Klinikum rechts der Isar (TU München)
  • München, Germany
    • Klinikum der Universität München (LMU)
  • Münster, Germany
    • Universitätsklinikum Münster
  • Nuremberg, Germany
    • Paracelsus Universität - Klinikum Nürnberg
  • Regensburg, Germany
    • Universitätsklinikum Regensburg
  • Tübingen, Germany
    • Universitätsklinikum Tübingen
• Italy
  • Bologna, Italy
    • S.Orsola-Malpighi Hospital
  • Milano, Italy
    • Ospedale San Raffaele SRL
• Netherlands
  • Maastricht, Netherlands
    • Maastricht University Medical Center
• Poland
  • Warsaw, Poland
    • Medical University of Warsaw
  • Zabrze, Poland
    • Silesian Center for Heart Diseases
• Sweden
  • Malmö, Sweden
    • Lund University Hospital Malmoe
  • Örebro, Sweden
    • Orebro University Hospital
• Switzerland
  • Bern, Switzerland
    • Bern University Hospital
• United Kingdom
  • London, United Kingdom
    • St Bartholomews Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MISACE arm; 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; 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.
No Intervention: control arm; 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

Collaborators and Investigators

• Sponsor: University of Leipzig
• Collaborators: German Research Foundation; Baylor College of Medicine; University of Pennsylvania; Rigshospitalet, Denmark; Universidad de Granada; European Commission; European Society of Cardiology; European Clinical Research Infrastructure Network; Modus Research and Innovation Limited
• Investigators: Principal Investigator: Christian D Etz, Prof. Dr., University Leipzig

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2018
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: January 12, 2018
• First Submitted That Met QC Criteria: February 8, 2018
• First Posted (Actual): February 15, 2018

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: TEVAR; SCI; Spinal cord injury; Staging; Stanford type B aortic dissection; Paraplegia; Embolization; Aortic Aneurysm Repair; TAAA; Thoracoabdominal aortic aneurysm; MISACE; Spinal cord ischemia; Spinal cord ischaemia; Spinal cord ischemic injury; Spinal cord ischaemic injury; Permanent paraplegia; Temporary paraplegia; Paraparesis; TAAA repair; Open TAAA repair; Open surgical TAAA repair; Endovascular TAAA repair; Aortic surgery; Thoracoabdominal aortic surgery; Type B aortic dissection; Chronic type B aortic dissection; Collateral network; Paraspinal collateral network; Paraspinous collateral network; Arteriogenesis; Intercostal arteries
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neurologic Manifestations; Paralysis; Aortic Diseases; Aortic Aneurysm, Abdominal; Aneurysm; Aortic Aneurysm; Paraplegia; Aortic Aneurysm, Thoracoabdominal
• Other Study ID Numbers: PAPAartis; 733203 (Other Grant/Funding Number: Horizon2020, European Commission); ET 127/2-1 (Other Grant/Funding Number: German Research Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No