Tacrolimus Reduction for Liver Transplant

(iSYNAPSE Trial)

This trial explores whether reducing the medication tacrolimus (an immunosuppressant drug) by 50% is effective for children who have had liver transplants. Researchers aim to determine if a lower dose can maintain liver health without causing harm. The trial seeks participants who received their liver transplant at a young age and have had stable liver function without recent rejection issues. Participants will gradually reduce their tacrolimus dose while doctors monitor their liver health over 18 months.

As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

The trial does not specify if you need to stop taking your current medications, but it requires that you have been on tacrolimus monotherapy for more than 6 months. If you are taking other medications that could affect the study, the investigator might ask you to stop them.

Research has shown that using low doses of tacrolimus over an extended period is generally safe for liver transplant patients. One study found that after a year, patients on low-dose tacrolimus did not experience severe rejection of their new liver, and infections and other side effects remained manageable. Another study demonstrated that using only tacrolimus soon after a liver transplant is effective and has expert support. Importantly, both once-daily and twice-daily versions of tacrolimus are similarly safe and effective. While some studies mention that varying blood levels of tacrolimus can cause issues, the treatment is overall well-tolerated. Tacrolimus already has approval for use in liver transplants, further supporting its safety.¹²³⁴⁵

Most treatments for liver transplant patients involve maintaining a consistent dose of immunosuppressants like tacrolimus to prevent organ rejection. However, the current trial explores a new protocol that reduces the tacrolimus dose by up to 50%. This reduction could potentially minimize the side effects associated with long-term immunosuppression, such as kidney damage and increased infection risk. Researchers are excited because this approach may offer a safer, more sustainable way to manage post-transplant health without compromising the effectiveness of the transplant.

Research has shown that tacrolimus helps prevent organ rejection after liver transplants. One study found that using low doses of tacrolimus over a long period was safe and effective for liver transplant recipients. Another study demonstrated that tacrolimus maintained patient survival rates at about 90% and graft survival rates at about 85% over a year. This trial will explore the effects of reducing tacrolimus doses by 50% in eligible participants. These findings suggest that lowering tacrolimus doses might still prevent organ rejection while potentially reducing side effects.¹³⁴⁶⁷