With all the devastation that the COVID-19 pandemic has wrought, 2020 ended with news of major triumphs for science and medicine. First, we saw the historic start of vaccine administration for two COVID-19 vaccines. Now, despite tremendous barriers to conducting clinical research during the pandemic, the Johns Hopkins All Children’s Hospital-led, National Institutes of Health (NIH)-sponsored multinational Kids-DOTT clinical trial has successfully been completed.
Opened to its first patient enrollments in 2007, Kids-DOTT is a landmark randomized clinical trial on the duration of anti-clotting medication (anticoagulant) therapy for venous thromboembolism (VTE) in patients under 21 years old. In late December and early January, one-year follow-up visits for the primary efficacy and safety endpoints were performed at two collaborating institutions where the last patients in the trial had been enrolled — Children’s Hospital Los Angeles and Children’s Healthcare of Atlanta.
VTE, which includes blood clots in the deep veins of the legs, arms, other areas of the body, is an infrequent but potentially life-threatening acute medical condition in children and young adults. The significance of VTE in young patients has drawn increased awareness during the COVID-19 pandemic, given emerging data on a greatly increased rate of VTE among children who are hospitalized with severe COVID-19 illness, including the multisystem inflammatory syndrome in children (MIS-C) form of the disease.
George Jallo, M.D., professor of Neurosurgery and Pediatrics at Johns Hopkins University School of Medicine, vice dean for Johns Hopkins All Children’s, and director of the Johns Hopkins All Children’s Institute for Brain Protection Sciences, says, “It is fitting that the Kids-DOTT trial investigator group and faculty colleagues in the Johns Hopkins All Children’s Institute for Clinical and Translational Research have recently launched a second and very timely national clinical trial, called COVAC-TP, designed to determine the optimal dosing, safety and preliminary efficacy of anticoagulation for the prevention of VTE in children hospitalized for COVID-19 (including MIS-C). That trial is also well on its way toward an anticipated successful completion.”
The Kids-DOTT trial’s leader, Neil Goldenberg, M.D., Ph.D., professor of Pediatrics and Medicine at Johns Hopkins University School of Medicine, associate dean for research at Johns Hopkins All Children’s in St. Petersburg, Florida and director of the Johns Hopkins All Children’s Institute for Clinical and Translational Research, says, “The tremendous success in conducting Kids-DOTT in recent years reflects the collective efforts of a talented team of clinical research professionals in the institute and associated research cores on this campus, over a hundred collaborating investigators, study coordinators, and research nurses in the U.S., Canada, Europe and beyond, and several hundred pediatric patients and their parents from around the world.”
Goldenberg adds, “We are tremendously grateful to all those who have contributed to this historical trial, which has also given rise to a unique biobank in the field of pediatric VTE of over 10,000 blood-derived specimens of plasma, DNA and RNA, maintained in the state-of-the-art, College of American Pathologists accredited Johns Hopkins All Children’s Pediatric Biorepository. Furthermore, through the trial’s existing grant funding from the NIH, a large subgroup of patients enrolled in the trial will continue to be followed long-term, in order to assess secondary efficacy and safety outcomes at two years post-diagnosis of acute VTE.”
Conceived in 2002 when Goldenberg was a resident in Internal Medicine and Pediatrics at the University of South Florida, the Kids-DOTT trial has been continuously supported by multiple grants since 2004, including a Thrombosis Studies Award from the Hemophilia and Thrombosis Research Society of North America, an NIH K23 Career Development Award, a Bridge Grant from the American Society of Hematology, an Institutional Research Grant from the Johns Hopkins All Children’s Foundation, two U01 Independent Investigator Awards from the NIH, and an NIH Diversity Supplement Award.
Kids-DOTT is one of the largest clinical trials ever conducted in the field of pediatric thromboembolism. Once database closure and analysis procedures have been completed, the main results of the trial are anticipated to be reported in spring 2021.