SAXOPHONE

(Phase 2, open-label 2:1 randomized trial of apixaban vs. standard of care)

Study Summary

Safety of Apixaban on pediatric heart disease on the prevention of embolism

People with certain types of heart disease may need to take medication to prevent their blood from clotting. That medication is called an anticoagulant or a blood thinner. The purpose of this study was to find out whether the medicine called apixaban (commonly known as Eliquis®) is safe for children with heart disease, and to learn how much apixaban will be present in the blood after taking a certain dose. Researchers compared apixaban to two other widely used blood thinners in children with congenital or acquired heart disease.

192 Children

with heart disease who needed to take medication to prevent blood clots

No Safety Concerns

Bleeding and thromboembolism were infrequent in both treatment groups.

Apixiban a Good Treatment Option

Results support the use of apixaban as an alternative for thromboprophylaxis in pediatric heart disease.

Who was in the study?

From 2017 to 2021, 192 participants ages 28 days to 17 years with congenital or acquired heart disease who needed to take medication to prevent blood clots were enrolled and randomized.

What happened during the study?

Participation lasted for up to 14 months, or until anticoagulation was no longer needed.  The study consisted of:

  1. Screening: physical examination, including heart rate, blood pressure, body temperature, height and weight, and blood draw for laboratory tests. Children 5 years and older had a bone density scan.
  2. Randomization: Children were randomly assigned to receive either apixaban (by mouth or feeding tube) or to receive one of the blood thinners commonly used to treat this condition: either VKA or LMWH. Older participants were also be asked to answer survey questions about quality of life. A blood sample was requested.
  3. Treatment: Participants took the study medication for 12 months, or until they no longer need a blood thinner. Return visits to the study center occurred at 2 weeks, 3 months, 6 months, 12 months and 14 months after beginning treatment. Visits included a physical examination, blood draw for laboratory tests, and questions about side effects, adverse events, and blood clots or bleeding. Some visits also included a bone density scan and quality of life questionnaires. The study center also called to check up on the child after 8 months and 10 months of treatment.

What were the results of the study?

One apixaban participant (0.8%) and 3 with other standard treatments (4.8%) had major or clinically relevant nonmajor bleeding (% difference -4.0 [95% CI: -12.8 to 0.8]). Apixaban incidence rate for all bleeding events was nearly twice the rate of other treatments (100.0 vs 58.2 per 100 person-years), driven by 12 participants with ≥4 minor bleeding events. No thromboembolic events or deaths occurred in either group. Apixaban pediatric PK steady-state exposures were consistent with adult levels.

In this pediatric multinational, randomized trial, bleeding and thromboembolism were infrequent. These results support the use of apixaban as an alternative for thromboprophylaxis in pediatric heart disease.

Study Publications

  • A multi-national trial of a direct oral anticoagulant in children with cardiac disease: Design and rationale of the Safety of ApiXaban On Pediatric Heart disease On the preventioN of Embolism (SAXOPHONE) study

    R. M. Payne, Am Heart J. 2019 Nov;217:52-63.

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  • Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease

    R. M. Payne, JACC. 2023 Dec, 82 (24)2296-2309.

    Children with heart disease sometimes need blood thinners to avoid strokes or other heart problems. Until now, the only blood thinners we had to use were warfarin and an injectable form of heparin, which we also use in adults for the same purpose. However, children are hard to treat with these drugs because they are so active, putting them at risk of bleeding, and because their diet may change, and this can change the level of blood thinner needed to keep them safe. In addition, we need to draw frequent blood samples in children to measure the blood thinner level and adjust the dosage. To get around these problems, we conducted an extensive worldwide trial of a new blood thinner called apixaban in children with heart disease. This blood thinner has already been approved for use in adults but has not been formally tested for use in children. This trial showed that apixaban was safe, well-tolerated for children, and as effective as the standard of care, warfarin, and heparin. No child had a stroke or cardiac problem during the trial. Additionally, apixaban does not require blood level monitoring and does not react or change depending on the child’s diet. This clinical trial also established the appropriate dose for children of different weights. This trial has helped to advance our care and treatment of children with heart disease and has made it safer to provide blood thinners for them.

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