Paraplegia Prevention in Aortic Aneurysm Repair by Thoracoabdominal Staging

Aortic Aneurysm, Thoracoabdominal Clinical Trial

— PAPAartis  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03434314
• Other study ID #: PAPAartis
• Secondary ID: 733203ET 127/2-1
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 8, 2018
• Est. completion date: June 2025

Study information

• Verified date: April 2024
• Source: University of Leipzig
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Thoracoabdominal
• Paraplegia

Intervention

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.

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Herzzentrum Hietzing	Vienna
France	University Hospital of Bordeaux	Bordeaux
France	Marie Lannelongue Hospital	Le Plessis-Robinson
Germany	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 der Universität München (LMU)	München
Germany	Klinikum rechts der Isar (TU München)	Munich
Germany	Universitätsklinikum Münster	Münster
Germany	Paracelsus Universität - Klinikum Nürnberg	Nuremberg
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Universitätsklinikum Tübingen	Tübingen
Italy	S.Orsola-Malpighi Hospital	Bologna
Italy	Ospedale San Raffaele SRL	Milano
Netherlands	Maastricht University Medical Center	Maastricht
Poland	Medical University of Warsaw	Warsaw
Poland	Silesian Center for Heart Diseases	Zabrze
Sweden	Lund University Hospital Malmoe	Malmö
Sweden	Örebro University Hospital	Örebro
Switzerland	Bern University Hospital	Bern
United Kingdom	St Bartholomews Hospital	London

Sponsors (10)

Lead Sponsor	Collaborator
University of Leipzig	Baylor College of Medicine, European Clinical Research Infrastructure Network, European Commission, European Society of Cardiology, German Research Foundation, Modus Research and Innovation Limited, Rigshospitalet, Denmark, Universidad de Granada, University of Pennsylvania

Countries where clinical trial is conducted

Austria,  France,  Germany,  Italy,  Netherlands,  Poland,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	mortality	all-cause mortality	at 30 days and one year after TAAA repair
Secondary	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
Secondary	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
Secondary	sub-group analyses	sub-group analyses of mortality for open repair and endovascular repair separately	up to one year after TAAA repair
Secondary	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
Secondary	cross-clamping times	cross-clamping times during open surgery	during open surgery
Secondary	residual aneurysm sac perfusion	residual aneurysm sac perfusion, i.e. type II endoleaks (only for endovascular repair)	up to one year after TAAA repair
Secondary	costs	incremental cost-effectiveness ratio (ICER) will be calculated	up to one year after TAAA repair
Secondary	Quality Adjusted Life Years	Quality Adjusted Life Years (QALYs) will be estimated over one year	up to one year after TAAA repair