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Active, not recruitingNCT03434314PAPAartisUpdated Apr 11, 2024

Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging

An interventional study of Minimally-Invasive Segmental Artery Coil-Embolization in Aortic Aneurysm, Thoracoabdominal, sponsored by University of Leipzig. Active, not recruiting at 29 sites in 9 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-11.

Sponsored by University of Leipzig · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
500
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • TAAA, Crawford type II or III
  • planned open or endovascular repair of aneurysm within four months
  • ≥ 18 years old

Exclusion criteria

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
500 participants (estimated)

Study arms

  • 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

  • No intervention
    control arm

    receives treatment of aneurysm as usual: open surgical repair or endovascular repair without MISACE

Interventions

  • ProcedureMinimally-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.

05

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 30 days after TAAA repair

Secondary outcomes

  1. substantial spinal cord injury

    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

    Time frame: 30 days after TAAA repair and at one year after TAAA repair

  2. 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).

    Time frame: from date of TAAA repair and up to one year after TAAA repair

  3. mortality

    all-cause mortality

    Time frame: at 30 days and one year after TAAA repair

  4. stay in intensive care unit and intermediate care

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

    Time frame: from date of TAAA repair and up to one year after TAAA repair

  5. sub-group analyses

    sub-group analyses of spinal cord injury according to modified Tarlov scale (see above) for open repair and endovascular repair separately

    Time frame: up to one year after TAAA repair

  6. sub-group analyses

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

    Time frame: up to one year after TAAA repair

  7. re-operation for bleeding

    re-operation for bleeding (only for open repair)

    Time frame: from date of TAAA repair and up to one year after TAAA repair

  8. cross-clamping times

    cross-clamping times during open surgery

    Time frame: during open surgery

  9. residual aneurysm sac perfusion

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

    Time frame: up to one year after TAAA repair

  10. costs

    incremental cost-effectiveness ratio (ICER) will be calculated

    Time frame: up to one year after TAAA repair

  11. Quality Adjusted Life Years

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

    Time frame: up to one year after TAAA repair

06

Study locations

29 sites
  • Medizinische Universität Innsbruck
    Innsbruck, Austria
  • Herzzentrum Hietzing
    Vienna, Austria
  • University Hospital of Bordeaux
    Bordeaux, France
  • Marie Lannelongue Hospital
    Le Plessis-Robinson, France
  • Uniklinik RWTH Aachen
    Aachen, Germany
  • Deutsches Herzzentrum Berlin
    Berlin, Germany
  • Universitätsklinikum Düsseldorf
    Düsseldorf, Germany
  • Westdeutsches Herz und Gefäßzentrum Essen
    Essen, Germany
  • Universitäts-Herzzentrum Freiburg/ Bad Krozingen
    Freiburg, Germany
  • Herzzentrum Hamburg
    Hamburg, Germany
  • Medizinische Hochschule Hannover
    Hanover, Germany
  • Universitätsklinikum Heidelberg
    Heidelberg, Germany
  • Herzzentrum Leipzig
    Leipzig, Germany
  • UniversitätskIinikum Leipzig
    Leipzig, Germany
  • Klinikum rechts der Isar (TU München)
    Munich, Germany
  • Klinikum der Universität München (LMU)
    München, Germany
  • Universitätsklinikum Münster
    Münster, Germany
  • Paracelsus Universität - Klinikum Nürnberg
    Nuremberg, Germany
  • Universitätsklinikum Regensburg
    Regensburg, Germany
  • Universitätsklinikum Tübingen
    Tübingen, Germany
  • S.Orsola-Malpighi Hospital
    Bologna, Italy
  • Ospedale San Raffaele SRL
    Milano, Italy
  • Maastricht University Medical Center
    Maastricht, Netherlands
  • Medical University of Warsaw
    Warsaw, Poland
  • Silesian Center for Heart Diseases
    Zabrze, Poland
  • Lund University Hospital Malmoe
    Malmö, Sweden
  • Örebro University Hospital
    Örebro, Sweden
  • Bern University Hospital
    Bern, Switzerland
  • St Bartholomews Hospital
    London, United Kingdom
07

References and documents

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. PubMed 30837256 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03434314
Lead sponsor
University of Leipzig
Collaborators
European Commission, German Research Foundation, Universidad de Granada, European Clinical Research Infrastructure Network, Modus Research and Innovation Limited, Rigshospitalet, Denmark, European Society of Cardiology, Baylor College of Medicine, University of Pennsylvania
Responsible party
David Petroff (Dr. David Petroff [Prof. Dr. Christian Etz], University of Leipzig) — Principal investigator
First posted
Feb 15, 2018
Start date
Nov 8, 2018
Primary completion
Jun 2025 (estimated)
Completion
Jun 2025 (estimated)
Last update
Apr 11, 2024

Study contacts

Christian D Etz, Prof. Dr.
principal investigator · University Leipzig

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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