Enrollment has completed for a landmark randomized clinical trial at Johns Hopkins All Children’s on the duration of anti-clotting medication (anticoagulant) therapy for venous thromboembolism (VTE) in patients under 21 years old — the Kids-DOTT trial. A multinational biobank of blood samples for future discovery of disease biomarkers will be established as part of the study.
Founded in 1926, Johns Hopkins All Children’s was the first children’s hospital in the state of Florida. In 1916 there were more than 27,000 cases and 6,000 deaths due to polio throughout the United States. There was no treatment nor cure for polio, which returned in epidemics and outbreaks every summer for more than 50 years. There was only quarantine — and in Florida, those without resources could end up at poor farms, working largely without wages or medical care. American Legion members signed a charter in December 1926 to create a new facility and new approach to community health focused on compassionate pediatric care, provided without regard for race, religion or ability to pay. Today Johns Hopkins All Children’s Hospital provides expert pediatric care for infants, children and teens with some of the most challenging medical problems in the community and around the world.
VTE, which includes blood clots in the deep veins of the legs, arms, other areas of the body, including those that travel to (or originate in) the arteries of the lungs, occurs in only about 1 in 10,000 children — clearly, an infrequent health condition. However, among hospitalized children, VTE occurs in 1 in 200 children with critical illnesses, making it one of the most common hospital-acquired pediatric conditions. Another all-too-common scenario for pediatric VTE is the use of estrogen-containing oral contraceptive pills in adolescent females who are overweight or have a history of VTE in family members who are middle-aged or younger.
The Kids-DOTT trial design is innovative in that it incorporates both a randomized trial as well as two parallel observational cohort arms that track outcomes in patient subgroups that don’t meet criteria for randomization. This provides efficiency in a relatively low-frequency health condition like pediatric VTE by taking advantage of the infrastructure of a large randomized trial and its “economy of scale” to establish much-needed data on natural history in subpopulations of interest for future randomized trials.
Children receive the same treatment standard of care as adults, however the efficacy of this treatment has not been confirmed in clinical trials for pediatric patients. The Kids-DOTT trial design is innovative in that it incorporates both a randomized trial as well as two parallel observational cohort arms that track outcomes in patient subgroups that don’t meet criteria for randomization. This provides efficiency in a relatively low-frequency health condition like pediatric VTE by taking advantage of the infrastructure of a large randomized trial and its “economy of scale” to establish much-needed data on natural history in subpopulations of interest for future randomized trials.
As well as the biobank additional innovations of the trial include: its use of a nested pilot/feasibility phase with pre-specified criteria to be met prior to continuing seamlessly into the rest-of-trial phase of the definitive study; and its use of real-time centralized remote monitoring of all eligibility/ randomization criteria of enrollees across more than 50 participating centers.
With a total enrollment of 607 patients altogether in the randomized trial and parallel cohorts, Kids-DOTT is the largest trial ever conducted in the field of pediatric thromboembolism. With a follow-up period of one year for patient outcomes, followed by database closure and analysis procedures, the main results of the trial are anticipated to be reported in Spring 2021.
“While the Kids-DOTT story is still being written, it’s clear that its main heroes are the children, young adults, and parents who have generously participated in the trial for the benefit of future young patients with VTE.” … “The other heroes who too often go unrecognized are the experienced, highly-trained clinical research professionals who work closely with the physician-investigators, patients and parents at each of the participating centers in the trial — as well as those at the coordinating center at Johns Hopkins All Children’s who support their peers at all participating centers — to ensure the safety of the patient participants and the integrity of the trial.” – Neil Goldenberg, M.D., Ph.D., principal investigator for Kids-DOTT
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