The primary objective is to greatly reduce incidence of ischaemic spinal cord injury (SCI, potentially resulting in permanent paraplegia) and mortality - the most devastating complications resulting from open surgical and thoracoabdominal…
ID
Source
Brief title
Condition
- Aneurysms and artery dissections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
Successful treatment of the aneurysm. That means:
• The patient is alive and without substantial SCI 30 days after treatment, and
• the aneurysm did not rupture and has been excluded within six months of
randomization.
Secondary outcome
The secondary objective of the trial will focus on further potential treatment
advantages and/or risks of the MIS2ACE-procedure.
Secondary endpoints:
• substantial SCI at 30 days after TAAA repair and at one year
• SCI according to the modified Tarlov scale from TAAA repair to one year
• all-cause mortality at 30 days and one year after TAAA repair
• length of stay in intensive care unit (ICU) and intermediate care unit (IMCU)
after TAAA repair
• sub-group analyses for open repair and endovascular repair separately
• re-operation for bleeding (only for open repair)
• cross-clamping times during open surgery
• residual aneurysm sac perfusion, i.e. type II endoleaks (only for
endovascular repair)
• costs and Quality Adjusted Life Years (QALYs) will be estimated over one year
Safety endpoints:
• kidney failure
• respiratory failure
• embolic events
Background summary
Based on statistics from the USA, one can estimate that 7,500 people per 100
Mio are diagnosed annually with an aortic aneurysm. Left untreated, the
prognosis is very poor, since internal bleeding due to a rupture of the
aneurysm brings about sudden death. If diameters have reached 60 mm, mortality
is estimated to be 11%/year.
The repair of aortic aneurysms is based on conventional stenting techniques.
There are three surgical approaches:
• Open TAAA repair involves surgical removal of a section of the aorta and
replacing it with a vascular prosthesis.
• Endovascular approach is a much less invasive approach. Small incisions are
made to access blood vessels in the groin. A catheter is inserted and used to
deploy a stent graft within the aneurysm.
• Hybrid approaches use a combination of these two techniques.
These methods have achieved a remarkable decrease in the incidence of
paraplegia and paraparesis, but they still constitute an incidence of up to 20%.
At present there is a tremendous need for state of the art and safe strategies
for aortic repair which prevent paraplegia - an individual disaster with
profound impact on long-term outcomeand health care cost
Study objective
The primary objective is to greatly reduce incidence of ischaemic spinal cord
injury (SCI, potentially resulting in permanent paraplegia) and mortality - the
most devastating complications resulting from open surgical and
thoracoabdominal endovascular aneurysm repair.
Study design
PAPAartis is a multi-national, prospective, open-label, two-arm randomized
controlled phase II b trial to demonstrate that a minimally-invasive taged
treatment approach can dramatically reduce paraplegia and mortality in patients
undergoing thoracoabdominal aortic aneurysm repair.
Intervention
Experimental group: Minimally-Invasive Staged Segmental Artery
Coil-Embolization (MIS2ACE, one up to three stages) prior to open surgical
repair and/or endovascular repair
Duration of intervention per patient: one up to three sessions of ca. 45 minutes
Control group: receives treatment of aneurysm as usual - open surgical repair
and/or endovascular repair without MIS2ACE
Follow-up per patient: one year after TAAA repair Individual treatment period:
12-18 months including follow-up (depends on group)
Study burden and risks
With the exception of trial-specific visits 0, 1 and 4, the treatment will be
performed according to standard treatment of an aortic aneurysm as part of the
study. For these visits (0/1/4) trial-specific blood samples are required as
listed above. It is extremely rare for blood withdrawal to result in
haematomas, vascular injuries or nerve injuries, which in some cases can also
lead to long-lasting damage. However, care is taken to avoid these
complications.
Further examinations of these visits, such as blood pressure measurements,
electrocardiogram and neurological examinations are usually without risk.
Trial-specific risks that only affect the MIS2ACE group:
As a result of treatment with the coils/plugs adverse events may occur. There
is a possibility that the aneurysm may rupture in between the time prior to the
aneurysm repair, which may be several weeks longer in the MIS2ACE group.
The placement of a catheter will occur multiple times as part of the standard
care for aneurysm repair. As part of the MIS2ACE treatment, up to three further
catheterizations are performed. As a result of the catheter placement, small
hematomas and mild pain can occur at the point of entry. Very rarely, bleeding,
vascular injuries and the formation of blood clots and fistulas can occur,
especially at the puncture site. The rupture and detachment of plaques or blood
clots can lead to vascular occlusion.
Although it has never occurred in previous preclinical and clinical trials, it
cannot be excluded that the insertion of the coils/plugs causes paraplegia.
The insertion of the coils/plugs takes place under X-ray control and use of
contrast agents. X-ray inspection exposes the patients to a maximum of about 20
mSv of radiation as a result of one MIS2ACE treatment. This corresponds to
approximately 10-fold of the natural radiation exposure per year in Germany
(2.1 mSv). If the patient receives three MIS2ACE treatments, that would
correspond to 30-fold of the natural radiation exposure per year in Germany.
Contrast agents can lead on the one hand to allergies and be problematic on the
other hand for patients with impaired kidney function. Renal function is
therefore continuously monitored in the trial. Patients with stage 4 chronic
renal failure are not included in the study.
Strümpellstraße 39
Leipzig 04289
DE
Strümpellstraße 39
Leipzig 04289
DE
Listed location countries
Age
Inclusion criteria
• TAAA, Crawford type I, II or III or type B dissections of comparable extent
• 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 (patients with a previous
successful aortic arch aneurysm repair may be included
independent of technique used)
• 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 (*shaggy* aorta, i.e.
prominent thromboembolic or atherosclerotic debris)
• severe contrast agent allergy, severe reduction in glomerular
filtration rate (CKD stage 4)
• expected lack of compliance (e.g. if the patient may not be
willing to have several MIS2ACE sessions and the following
repair)
• 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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03434314 |
| CCMO | NL69212.068.19 |