Clinical trials

Ischemic heart disease (IHD) leads the global mortality statistics. Atherosclerotic plaques in coronary arteries hallmark IHD, drive hypoxia, and may rupture to result in myocardial infarction (MI) and death of contractile cardiac muscle, which is eventually replaced by a scar. Depending on the extent of the damage, dysbalanced cardiac workload often leads to emergence of heart failure (HF). The atrial appendages, enriched with active endocrine and paracrine cardiac cells, has been characterized to contain cells promising in stimulating cardiac regenerative healing. In this AAMS2 randomized controlled and double-blinded trial, the patient's own tissue from the right atrial appendage (RAA) is for therapy. A piece from the RAA can be safely harvested upon the set-up of the heart and lung machine at the beginning of coronary artery bypass (CABG) surgery. In the AAMS2 trial, a piece of the RAA tissue is processed and utilized as epicardially transplanted atrial appendage micrografts (AAMs) for CABG-support therapy. In our preclinical evaluation, epicardial AAMs transplantation after MI attenuated scarring and improved cardiac function. Proteomics suggested an AAMs-induced glycolytic metabolism, a process associated with an increased regenerative capacity of myocardium. Recently, the safety and feasibility of AAMs therapy was demonstrated in an open-label clinical study. Moreover, as this study suggested increased thickness of the viable myocardium in the scarred area, it also provided the first indication of therapeutic benefit. Based on randomization with estimated enrolment of a total of 50 patients with 1:1 group allocation ratio, the piece of RAA tissue is either perioperatively processed to AAMs or cryostored. The AAMs, embedded in a fibrin matrix gel, are placed on a collaged-based matrix sheet, which is then epicardially sutured in place at the end of CABG surgery. The location is determined by preoperative late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRI) to pinpoint the ischemic scar. The controls receive the collagen-based patch, but without the AAMs. Study blood samples, transthoracic echocardiography (TTE), and LGE-CMRI are performed before and at 6-month follow-up after the surgery. The trial's primary endpoints focus on changes in cardiac fibrosis as evaluated by LGE-CMRI and circulating levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Secondary endpoints center on other efficacy parameters, as well as both safety and feasibility of the therapy.

The purpose of this study is to determine whether patients with operatively treated acetabular fractures benefit from early weight-bearing as tolerated. The study compares two groups ( n = 25 each), which are randomised into either weight-bearing as tolerated or touch-down weight-bearing for 6-8 weeks postoperatively. Both study groups are stratified according to * Type of fracture (anterior approach vs anterior + additional posterior approach) * Dislocated dome vs non-dislocated/ non existing separate dome fragment Patients, who are eligible to participate in the trial but choose not to participate in randomisation are asked to enrol in a prospective cohort follow-up cohort. This is to examine a potential participation bias in the RCT groups. These patients will not be counted into the target amount of 50 RCT patients.