Organ transplantation has been shown to prolong survival and improve quality of life for children and adults suffering from a range of congenital and acquired diseases. However, outcomes vary by pre-transplant diagnosis, comorbidities, and organ transplanted. Normal life expectancy and health-related quality of life are rarely, if ever, achieved after organ transplantation. Although 1-year survival after organ transplantation has continuously improved, the prevalence of morbidities such as infection, systemic hypertension, diabetes mellitus, renal insufficiency, and malignancy remain higher in transplant recipients than in the general population. The barriers to success of organ transplantation predominantly include: 1) immunologic incompatibility between donor and recipient leading to acute and chronic rejection; and 2) complications of long-term pharmacologic immune suppression.
The Clinical Trials in Organ Transplantation (CTOT) and Clinical Trials in Organ Transplantation in Children (CTOT-C) consortia were established in 2004 and 2008, respectively, to accelerate meaningful clinical and mechanistic studies of the immune-mediated morbidity associated with organ transplantation in adults and children. In 2021, CTOT and CTOT-C were combined to form Clinical Trials in Organ Transplantation in Children and Adults (CTOT-CA). With the participation of approximately 200 clinical sites and core laboratories, these consortia have enrolled nearly 7000 participants to conduct 33 multi-center clinical studies in organ transplantation, including:
- Nine randomized clinical trials
- Four phase I-II single-arm interventional studies
- Nine biomarker development/validation studies
- Eleven observational studies of immune mechanisms/clinical outcomes
All CTOT, CTOT-C, and CTOT-CA studies have harmonized clinical data collection, as well as the timing of and methods used for mechanistic assays, thus creating a powerful data resource for exploratory and confirmatory analyses.
Main Areas of Focus
CTOT-CA investigates the immunologic and infectious barriers to long-term transplantation success by conducting interventional clinical trials (Phase I, II, or III) and observational studies in heart, kidney, lung, and liver transplantation. The goals of this research are to further our understanding of and ultimately reduce immune- and infection-mediated morbidity and mortality in organ transplantation.
Currently Funded Awards
Boston Children’s Hospital
Principal Investigator: David Briscoe
Grant Number: U01AI163072
Duke University
Principal Investigator: Stuart Knechtle
Grant Number: U01AI163065
Duke University
Principal Investigators: Scott Palmer, John Belperio
Grant Number: U01AI163099
Massachusetts General Hospital
Principal Investigators: Joren Madsen, Ramsey Hachem, Daniel Kreisel
Grant Number: U01AI163086
Northwestern University
Principal Investigator: Justin Boike, Paolo Cravedi
Grant Number: U01AI163081
University of Pennsylvania
Principal Investigators: Ali Naji, Vijay Bhoj, Alfred Garfall, Carl June, James Francis Markmann, Michael Milone
Grant Number: U01AI163087
University of California San Francisco
Principal Investigators: Abhijit Prakash Limaye, Don Diamond, Cynthia Fisher
Grant Number: U01AI163090