Expanding Heart Transplants from Donors After Circulatory Death (DCD) - Results of the First Randomized Controlled Trial Using the Organ Care System (OCS™) Heart - (OCS DCD Heart Trial)

Purpose To evaluate the effectiveness of the OCS Heart technology to resuscitate, preserve and assess DCD hearts for transplantation. Methods OCS DCD Heart Trial included the following donor inclusion criteria: Maastricht Category III DCD donor, donor age 18-49 years old, warm ischemic time (WIT) ≤30 mins. Donor exclusions: Previous history of cardiac surgery, coronary artery disease, cardiogenic shock, or myocardial infarction, terminal EF of ≤50%, or significant valve disease. Recipient inclusion criteria: primary adult heart transplant candidates. Recipient exclusion: multi-organ transplant candidates, history of prior solid organ or bone marrow transplants, history of chronic renal failure, or unrandomized recipients. Candidates were randomized 3:1 into two groups: DCD Heart Possible (DCD) or DBD cold stored hearts (Control). The trial protocol final analysis was prespecified to compare the post-transplant outcome from recipients of DCD hearts preserved on OCS (DCD) to all those who received DBD hearts preserved with cold storage (DBD Control). Endpoints Patient survival at 6- and 12-months post-transplantation. Other endpoints included; OCS DCD hearts utilization rate defined as the number of DCD hearts transplanted after OCS perfusion divided by the total number of eligible DCD donor hearts that were instrumented on OCS, incidence of severe left or right ventricular ISHLT PGD. Safety endpoint was defined as the incidence of Heart Graft-related Serious Adverse Events (HGRSAEs) in the first 30 days post-transplant defined as moderate or severe left or right ventricular ISHLT PGD, or primary graft failure requiring re-transplantation. Results A total of 180 patients were randomized and transplanted in the trial (DCD-OCS n=90 and Control-DBD n=90) at 13 heart transplant centers in the U.S. between 2019 and 2020. There was a total of 101 DCD donor hearts instrumented on OCS Heart technology, of those 90 were transplanted for an overall DCD hearts utilization rate of 89% (90/101). Donors and Recipients' demographics and risk factors were similar between the two arms except for age (donors- DCD 29.3 ± 7.5 vs Control 33.2 ± 11.4) (recipients- DCD-OCS 51.3 ± 12.6 vs Control-DBD 55.0 ± 11.4 p=0.041). Patient survival at 6 months was DCD 94.4% vs Control 88.6% p<0.0001, and graft survival at 6 months was DCD 98.9% vs Control 96.7% from K-M analysis. Patient survival at 1 year was DCD 93.3% vs Control 87.3%, and graft survival at 1 year was DCD 97.7% vs Control 96.7% from K-M analysis. Safety endpoint was similar between both trial arms DCD 0.2 HGRSAE per patient vs Control 0.1 HGRSAE per patient. Incidence of moderate or severe ISHLT PGD was 20% in DCD arm vs. 9.1% in Control arm. Incidence of primary graft failure was 0% in the DCD arm vs 2.2% in Control. Conclusion The OCS DCD Heart trial was the first ever randomized trial comparing DCD heart transplant to DBD standard criteria heart transplant clinical outcomes. The trial demonstrated that the use of OCS Heart resulted in high rate of DCD heart utilization for transplantation with excellent patient and graft survival outcomes compared to DBD donor hearts. These results support the increased use of DCD hearts for transplantation to expand the pool of donor hearts for transplantation.Kaplan-Meier Analysis of Patient & Graft Survival. To evaluate the effectiveness of the OCS Heart technology to resuscitate, preserve and assess DCD hearts for transplantation. OCS DCD Heart Trial included the following donor inclusion criteria: Maastricht Category III DCD donor, donor age 18-49 years old, warm ischemic time (WIT) ≤30 mins. Donor exclusions: Previous history of cardiac surgery, coronary artery disease, cardiogenic shock, or myocardial infarction, terminal EF of ≤50%, or significant valve disease. Recipient inclusion criteria: primary adult heart transplant candidates. Recipient exclusion: multi-organ transplant candidates, history of prior solid organ or bone marrow transplants, history of chronic renal failure, or unrandomized recipients. Candidates were randomized 3:1 into two groups: DCD Heart Possible (DCD) or DBD cold stored hearts (Control). The trial protocol final analysis was prespecified to compare the post-transplant outcome from recipients of DCD hearts preserved on OCS (DCD) to all those who received DBD hearts preserved with cold storage (DBD Control). Patient survival at 6- and 12-months post-transplantation. Other endpoints included; OCS DCD hearts utilization rate defined as the number of DCD hearts transplanted after OCS perfusion divided by the total number of eligible DCD donor hearts that were instrumented on OCS, incidence of severe left or right ventricular ISHLT PGD. Safety endpoint was defined as the incidence of Heart Graft-related Serious Adverse Events (HGRSAEs) in the first 30 days post-transplant defined as moderate or severe left or right ventricular ISHLT PGD, or primary graft failure requiring re-transplantation. A total of 180 patients were randomized and transplanted in the trial (DCD-OCS n=90 and Control-DBD n=90) at 13 heart transplant centers in the U.S. between 2019 and 2020. There was a total of 101 DCD donor hearts instrumented on OCS Heart technology, of those 90 were transplanted for an overall DCD hearts utilization rate of 89% (90/101). Donors and Recipients' demographics and risk factors were similar between the two arms except for age (donors- DCD 29.3 ± 7.5 vs Control 33.2 ± 11.4) (recipients- DCD-OCS 51.3 ± 12.6 vs Control-DBD 55.0 ± 11.4 p=0.041). Patient survival at 6 months was DCD 94.4% vs Control 88.6% p<0.0001, and graft survival at 6 months was DCD 98.9% vs Control 96.7% from K-M analysis. Patient survival at 1 year was DCD 93.3% vs Control 87.3%, and graft survival at 1 year was DCD 97.7% vs Control 96.7% from K-M analysis. Safety endpoint was similar between both trial arms DCD 0.2 HGRSAE per patient vs Control 0.1 HGRSAE per patient. Incidence of moderate or severe ISHLT PGD was 20% in DCD arm vs. 9.1% in Control arm. Incidence of primary graft failure was 0% in the DCD arm vs 2.2% in Control. The OCS DCD Heart trial was the first ever randomized trial comparing DCD heart transplant to DBD standard criteria heart transplant clinical outcomes. The trial demonstrated that the use of OCS Heart resulted in high rate of DCD heart utilization for transplantation with excellent patient and graft survival outcomes compared to DBD donor hearts. These results support the increased use of DCD hearts for transplantation to expand the pool of donor hearts for transplantation.Kaplan-Meier Analysis of Patient & Graft Survival.