NCT05955924

Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients - Pivotal Trial

Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients: a Multicentre, Pragmatic Randomized Trial

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 396 (estimated)
• Sponsor: Women's College Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

As patients live longer after receiving an organ transplant, there is a need to reduce the long-term side effects of the drugs used to prevent organ rejection. In particular, long-term use of these drugs increases the risk of skin cancer. Skin cancer is now a leading cause of illness and disfigurement after kidney, liver, heart, and lung transplantation. Given the increased risk and burden of skin cancer in transplant recipients, prevention is critical. Nicotinamide is a form of Vitamin B3 that has been shown to protect against skin cancer in the general population. However, it is unclear whether nicotinamide is effective among immune-suppressed transplant recipients. Investigators will conduct a clinical trial involving multiple transplant centres in Canada to evaluate whether oral nicotinamide (500 mg twice daily) is effective and safe for preventing skin cancer. Investigators will recruit 396 high-risk adult kidney, liver, heart, and lung transplant patients who have previously had at least one skin cancer. Patients will receive nicotinamide or sham tablets for up to 4 years. The results will inform efforts to improve the long-term health of transplant recipients.

Detailed description

Improved survival after solid organ transplantation has created the need to better prevent the long-term adverse effects of immunosuppressant drugs in transplant survivors - particularly cancer development. Keratinocyte carcinoma (non-melanoma skin cancer) is by far the most common form of post-transplant malignancy and has a more aggressive clinical course than in the general population. Preventive measures are thus critical to reduce the burden of skin cancer in the high-risk transplant population. Nicotinamide is a low-cost, commercially available, over-the-counter Vitamin B3 derivative that has been found to safely reduce the rate of keratinocyte carcinoma in immunocompetent patients with a history of skin cancer. It is unclear whether its efficacy and safety translate to the immunosuppressed transplant population. Given this uncertainty, Investigators plan to build on our internal pilot study (N=120) to conduct the SPRINTR (Skin cancer PRevention with Nicotinamide in Transplant Recipients) pivotal trial to address these specific aims: Primary question: Does oral nicotinamide (500 mg twice daily) reduce the rate of further keratinocyte carcinoma compared with placebo when used in addition to standard care for up to 208 weeks in high-risk solid organ transplant recipients? Secondary questions: 1. What is the safety of nicotinamide when used in addition to standard care for up to 208 weeks in the transplant population? 2. What is the effect of nicotinamide on quality of life related to skin cancer? Investigators will conduct a multicentre, pragmatic, parallel group, investigator- and patient-blinded, randomized trial with a superiority framework. This pivotal trial will evaluate the efficacy and safety of oral nicotinamide versus placebo to prevent further keratinocyte carcinoma in 396 high-risk solid organ transplant recipients. Data from our previous internal pilot study (N=120 participants) will be combined with data from the current pivotal trial (N=276 additional patients) in the final analysis.

Conditions

• Non-melanoma Skin Cancer
• Carcinoma, Squamous Cell
• Carcinoma, Basal Cell
• Keratinocyte Carcinoma

Interventions

Type	Name	Description
DRUG	Nicotinamide	Oral nicotinamide (500 mg) twice daily
DRUG	Placebo	Matching placebo capsule twice daily

Timeline

• Start date: 2023-08-28
• Primary completion: 2027-08-01
• Completion: 2027-08-01
• First posted: 2023-07-21
• Last updated: 2025-02-21

Locations

7 sites across 1 country: Canada