Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients: a Multicentre, Pragmatic Randomized Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 396
- 试验地点
- 7
- 主要终点
- Time to first biopsy-confirmed keratinocyte carcinoma (basal cell carcinoma or invasive cutaneous squamous cell carcinoma)
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Matching placebo
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old
- •Kidney, liver, heart, or lung transplant at least two years ago
- •History of at least one prior histologically-confirmed keratinocyte carcinoma or squamous cell carcinoma in situ
- •Currently immunosuppressed with a calcineurin inhibitor-based regimen (cyclosporine or tacrolimus)
- •Able to attend follow-up visits
排除标准
- •Use of nicotinamide or niacin (≥250 mg daily) within past 12 weeks
- •Untreated localized skin cancer at baseline (patient can enrol after skin cancer treatment)
- •Biopsy-confirmed acute rejection episode within the past 12 weeks
- •Active liver disease (high AST >3 times or bilirubin >1.5 times)
- •Severe kidney disease (estimated glomerular filtration rate <20 mL/min/1.73 m2)
- •Solid organ or hematologic malignancy, invasive melanoma, Merkel cell carcinoma, or metastatic skin cancer within the past five years
- •Pregnancy or lactation
- •Need for ongoing carbamazepine or primidone
- •Allergy to nicotinamide or any ingredient of the vitamin or placebo capsules
研究组 & 干预措施
Nicotinamide
Intervention Drug : Nicotinamide
干预措施: Nicotinamide (Drug)
Placebo
Intervention: Placebo Oral Capsule
干预措施: Placebo (Drug)
结局指标
主要结局
Time to first biopsy-confirmed keratinocyte carcinoma (basal cell carcinoma or invasive cutaneous squamous cell carcinoma)
时间窗: Up to 208 weeks
次要结局
- Time to first invasive squamous cell carcinoma during follow-up(Up to 208 weeks)
- Time to first basal cell carcinoma during follow-up(Up to 208 weeks)
- Time to multiple keratinocyte carcinomas over follow-up(Up to 208 weeks)
- Occurrence of adverse events during follow-up(208 weeks)
- Acute graft rejection (biopsy-confirmed)(208 weeks)
- Graft loss or retransplantation(208 weeks)
- High/low cyclosporine or tacrolimus blood concentration requiring dose adjustment(208 weeks)
- Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score(208 weeks)
- Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA)(208 weeks)
- Neurocognitive substudy - Proportion of participants with cognitive impairment(208 weeks)
- Neurocognitive substudy - Change from baseline in demographically-corrected T score for Hopkins Verbal Learning Test - Revised(208 weeks)
- Neurocognitive substudy - Change from baseline in demographically-corrected T score for Trail Making A and B(208 weeks)
- Neurocognitive substudy - Change from baseline in demographically-corrected T score for Controlled Oral Word Association(208 weeks)
- Neurocognitive substudy - Change from baseline in demographically-corrected T score for Animal Naming Task(208 weeks)
- Neurocognitive substudy - Change from baseline in demographically-corrected T score for Wechsler Adult Intelligence Scale-Fourth Edition-Canadian (WAIS-IV-CDN).(208 weeks)
- Neurocognitive substudy - Change from baseline in demographically-corrected T score for Digit Span subtest(208 weeks)