The need for a clinical trial like PAPAartis.
Patients with a major enlargement of the aorta (one of the main blood vessels of the body) called a thoracoabdominal aortic aneurysm (TAAA) – are at high risk of bleeding to death if the aneurysm is left untreated and ruptures.
Aneurysm repair is carried out in two ways: Either the dilated section of the aorta is removed and replaced with a vascular prosthesis or the doctor places a stent (a kind of a small tube) on the inside of the aorta. The stent takes the pressure off the wall and prevents it from further expansion and/or potential rupture. The procedures are well established.
However, like all medicinal procedures, there are some potential complications. The most severe known complication is spinal cord injury resulting in paraparesis (a weakness of voluntary movement of the legs) or paraplegia. Currently this affects about 10-20% of the patients undergoing aneurysm repair for TAAA.
Thus, to avoid debilitation caused by TAAA-repair, new strategies to reduce the risk of paraparesis and paraplegia due to the intervention are needed.
The researchers, who initiated and perform this project have developed a new therapeutic strategy to achieve this goal: a pre-treatment prior to aortic aneurysm repair, potentially preventing spinal cord injury. It is called: MISACE - Minimally invasive segmental artery coil embolization.
How does the MISACE technique work?
During the MISACE intervention so called segmental arteries (small blood vessels that are located around the aorta) are occluded with “coils” or “plugs” that are inserted using a catheter. These are routinely used in the field of neurosurgery.
The induced occlusion causes the body to build an alternative blood supply (known as a collateral network) to the spinal cord. In animal studies, this provided sufficient blood supply to the spinal cord during aneurysm repair to prevent spinal cord damage. There have also been promising results in human patients treated with this method.
What will the clinical trial investigate?
Because results from a small number of patients are not conclusive, and unforeseen risks may be significant, it is essential to prove the effectiveness and safety of the MISACE procedure to reduce the risk of spinal cord injury after TAAA treatment in a larger patient group.
PAPAartis will compare patients who have undergone the MISACE procedure prior to aneurysm repair (MISACE group) to patients who did not undergo the MISACE prior to aneurysm repair (control group). Thus, the trial will answer, if the MISACE pre-treatment prevents paraplegia/spinal cord injury in patients receiving an aortic aneurysm repair. Furthermore, the trial will investigate the safety of the MISACE procedure and the impact on the patient’s recovery/quality of life.
Footnote: Which treatment (control or MISACE) the patients receive in case of study participation is determined by a predetermined random procedure, comparable to the throwing of a coin; this is called randomization. The probability that a patient will receive the MISACE procedure in addition to the standard treatment is 50%.
What else will PAPAartis investigate?
As the MISACE therapy is new, we will gather information on a number practical issues around the therapy to help generate guidelines for the use of MISACE as a standard pre-treatment for aneurysm repair and will contribute to the scientific understanding of the formation collateral blood vessel networks. We will also investigate whether early signs of spinal cord damage can be detected by carrying out tests on cerebro-spinal fluid collected during the aneurysm repair operation. Finally, we will assess the impact of the MISACE pre-treatment on patients quality of life and the financial impact on society - we anticipate there will be considerable cost savings through reduced use of healthcare services by patients, lower pay-outs in disability insurance and reduced loss of economic output through unemployment due to disability.
What will happen after the project finishes?
We intend to generate a strong body of evidence on the medical, patient welfare and financial benefits of using the MISACE as pre-treatment of a TAAA-repair during the project. This will help experts around the world to choose the optimal treatment strategy for future patients.