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| ID | Type | Description | Link |
|---|---|---|---|
| 836031011 | Other Grant/Funding Number | ZonMw | |
| 2014-003691-23 | EudraCT Number |
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Imiquimod | Active Comparator | three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage |
|
| 5-Fluorouracil | Active Comparator | during 4 (consecutive) weeks twice daily. Prior to treatment: curettage |
|
| Ingenol mebutate 0.015% | Active Comparator | during 3 (consecutive) days once daily. Prior to treatment: curettage |
|
| MAL-PDT | Active Comparator | methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Imiquimod | Drug | three times a week once daily during 4 consecutive weeks. Prior to treatment: curettage |
|
| Measure | Description | Time Frame |
|---|---|---|
| treatment succes | 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). | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| treatment failure | proportion of participants with <75% reduction in number of AK lesions after 3 and 12 months post final treatment compared to baseline (<75% patient clearance at 3 and 12 months). | 12 months |
| Treatment succes at 3 months post treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Klara Mosterd, MD, PhD | Maastricht University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht UMC | Maastricht | Limburg | 6202 AZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35475852 | Derived | Ahmady S, Jansen MHE, Nelemans PJ, Kessels JPHM, Arits AHMM, de Rooij MJM, Essers BAB, Quaedvlieg PJF, Kelleners-Smeets NWJ, Mosterd K. Risk of Invasive Cutaneous Squamous Cell Carcinoma After Different Treatments for Actinic Keratosis: A Secondary Analysis of a Randomized Clinical Trial. JAMA Dermatol. 2022 Jun 1;158(6):634-640. doi: 10.1001/jamadermatol.2022.1034. | |
| 33476658 |
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| ID | Term |
|---|---|
| D055623 | Keratosis, Actinic |
| ID | Term |
|---|---|
| D011230 | Precancerous Conditions |
| D009369 | Neoplasms |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000077271 | Imiquimod |
| D005472 | Fluorouracil |
| C486592 | 3-ingenyl angelate |
| ID | Term |
|---|---|
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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|
| 5-fluorouracil | Drug | during 4 (consecutive) weeks twice daily. Prior to treatment: curettage |
|
|
| Ingenol mebutate | Drug | during 3 (consecutive) days once daily. Prior to treatment: curettage |
|
|
| methylaminolevulinate photodynamic therapy | Procedure | methylaminolevulinate photodynamic therapy; one session. Prior to treatment: curettage |
|
|
proportion of participants with ≥75% reduction in number of AK lesions at 3 months post final treatment (≥ 75% patient clearance at 3 months). |
| 3 months |
| complete lesion clearance | proportion of lesions with 100% clearance in all treated patients at 3 and 12 months post final treatment. | 12 months |
| SCC | Proportion of patients who develop a SCC in the treatment area during study follow-up. | 12 months |
| side effects | local skin reactions reported in patient diary, visual analogue score (VAS), Patient-reported adverse events | 12 months |
| Cosmetic outcome | based on a Cosmetic questionnaire, filled in on baseline, 3 + 12 months | 3 and 12 months |
| patient satisfaction | Skindex-29 questionnaire (quality of life) , Actinic Keratosis Quality of Life (AKQoL) questionnaire; filled in on baseline, 3 + 12 months | 12 months |
| treatment compliance | defined as the number of applied treatments as percentage of the number of prescribed treatments, based on patient diaries and weighing returned medication. | 3 months |
| Overall decrease in AK | Decrease in number AK from baseline per patient, at 3 and 12 months post final treatment. | 3 and 12 months |
| Cost-effectiveness | Healthcare/treatment costs | 12 months |
| Investigator Global Improvement Indices | Investigator Global Improvement Indices (IGII) at 3 and 12 months post final treatment. | 3 and 12 months |
| Number of new lesions | Number of new lesions at 3 and 12 months post final treatment | 3 and 12 months |
| Ahmady S, Jansen MHE, Nelemans PJ, Essers BAB, Kessels JPHM, Kelleners-Smeets NWJ, Mosterd K. The Effect of Four Approaches to Treat Actinic Keratosis on the Health-Related QOL, as Assessed by the Skindex-29 and Actinic Keratosis QOL. J Invest Dermatol. 2021 Jul;141(7):1830-1832. doi: 10.1016/j.jid.2020.12.023. Epub 2021 Jan 18. No abstract available. |
| 31961446 | Derived | Jansen MHE, Kessels JPHM, Merks I, Nelemans PJ, Kelleners-Smeets NWJ, Mosterd K, Essers BAB. A trial-based cost-effectiveness analysis of topical 5-fluorouracil vs. imiquimod vs. ingenol mebutate vs. methyl aminolaevulinate conventional photodynamic therapy for the treatment of actinic keratosis in the head and neck area performed in the Netherlands. Br J Dermatol. 2020 Oct;183(4):738-744. doi: 10.1111/bjd.18884. Epub 2020 Feb 19. |
| 30855743 | Derived | Jansen MHE, Kessels JPHM, Nelemans PJ, Kouloubis N, Arits AHMM, van Pelt HPA, Quaedvlieg PJF, Essers BAB, Steijlen PM, Kelleners-Smeets NWJ, Mosterd K. Randomized Trial of Four Treatment Approaches for Actinic Keratosis. N Engl J Med. 2019 Mar 7;380(10):935-946. doi: 10.1056/NEJMoa1811850. |
| D017437 |
| Skin and Connective Tissue Diseases |
| D006571 | Heterocyclic Compounds |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |