Topical Ingenol Mebutate Versus 5% 5-fluorouracil Versus 5% Imiquimod Versus Photodynamic Therapy in Treatment of Actinic Keratosis: a Multi-centre Randomized Efficacy and Cost-effectiveness Study
试验速览
- 阶段
- 4 期
- 入组人数
- 624
- 试验地点
- 1
- 主要终点
- treatment succes
研究概览
简要总结
A multi-centre randomised controled single blind clinical phase IV trial with the aim to determine the most effective treatment in terms of lesion reduction, costs and patient satisfaction in treatment of actinic keratosis (AK), when comparing topical treatment with photodynamic therapy (PDT), 5% 5-fluorouracil (5-FU) cream, 5% Imiquimod (IMI) cream and ingenol mebutate (IM) gel.
详细描述
Skin cancer is the most common cancer in Caucasians and therefore a major public health issue. Its incidence is increasing rapidly. Actinic keratosis (AK) is the most prevalent precancerous chronic skin condition. It can transform into squamous cell carcinoma (SCC). AK's generally arise in a skin area that has diffuse precancerous damage, a phenomenon called field cancerization. Because of its precancerous character, it is advised to treat AK and herewith prevent development into SCC. The most frequently used field-directed treatments in the Netherlands are photodynamic therapy (PDT), topical 5% f-fluorouracil (5% 5-FU) and topical 5% Imiquimod (5% IMI). Lately another topical product is approved by Dutch healthcare insurances: Ingenol mebutate (IM). Up to date, which treatment the patient will receive, does not rely on evidence-based-medicine, but generally on the preference of the physician. Current national and international guidelines state no clear recommendations for the best choice of therapy. The aim of this study determine which treatment is the most effective treatment in terms of lesion reduction, costs and patient satisfaction when comparing topical treatment with photodynamic therapy (PDT), 5% 5-fluorouracil (5-FU) cream, 5% Imiquimod (IMI) cream and ingenol mebutate (IM) gel, in treatment of actinic keratosis (AK).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
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
- •Patients older than 18 years
- •Fitzpatrick skintype I-IV
- •Clinically confirmed diagnosis of AK
- •One joint area of minimal 25 cm2 and maximal 100 cm2 of AK
- •Minimum of 5 AK lesions
- •AK Olsen grade I-III
- •Location: head/neck area
排除标准
- •Received any kind of treatment for AK in the past 3 months
- •(non)melanoma skin cancer in target area
- •Immuno-compromised status
- •Use of systemic retinoid in the past 3 months
- •Use of immunosuppressant drugs in the past 3 months and / or at time of treatment (such as oral glucocorticoids, cytostatic, antibodies, drug acting on immunophilins, interferon, opioids, Tumor Necrosis Factor (TNF) binding proteins, mycofenolate mofetil (MMF), biologic agents). inhalation corticosteroids / nasal corticosteroids are permitted.
- •Porphyria
- •Not able to give informed consent
- •Allergy to study drugs or peanut/nut/soy products
- •Pregnant and breastfeeding women
- •Female in child bearing potential not using contraceptive measures, during and till 3 months post-treatment
- •Genetic skin cancer disorders
- •Not understanding Dutch language
研究组 & 干预措施
5-Fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
干预措施: Ingenol mebutate (Drug)
Imiquimod
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
干预措施: 5-fluorouracil (Drug)
Imiquimod
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
干预措施: Ingenol mebutate (Drug)
Imiquimod
three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage
干预措施: methylaminolevulinate photodynamic therapy (Procedure)
5-Fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
干预措施: Imiquimod (Drug)
5-Fluorouracil
during 4 (consecutive) weeks twice daily. Prior to treatment: curettage
干预措施: methylaminolevulinate photodynamic therapy (Procedure)
Ingenol mebutate 0.015%
during 3 (consecutive) days once daily. Prior to treatment: curettage
干预措施: Imiquimod (Drug)
Ingenol mebutate 0.015%
during 3 (consecutive) days once daily. Prior to treatment: curettage
干预措施: 5-fluorouracil (Drug)
Ingenol mebutate 0.015%
during 3 (consecutive) days once daily. Prior to treatment: curettage
干预措施: methylaminolevulinate photodynamic therapy (Procedure)
MAL-PDT
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
干预措施: Imiquimod (Drug)
MAL-PDT
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
干预措施: 5-fluorouracil (Drug)
MAL-PDT
methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage
干预措施: Ingenol mebutate (Drug)
结局指标
主要结局
treatment succes
时间窗: 12 months
the proportion of patients with ≥75% lesion reduction in the number of AK lesions counted at baseline in the treatment area 12 months post final treatment (≥ 75% patient clearance at 12 months).
次要结局
- treatment failure(12 months)
- complete lesion clearance(12 months)
- Number of new lesions(3 and 12 months)
- SCC(12 months)
- Treatment succes at 3 months post treatment(3 months)
- side effects(12 months)
- patient satisfaction(12 months)
- treatment compliance(3 months)
- Cosmetic outcome(3 and 12 months)
- Overall decrease in AK(3 and 12 months)
- Investigator Global Improvement Indices(3 and 12 months)
- Cost-effectiveness(12 months)