Clinical trial NCT04814511: Escalated Therapy of Scabies With INFECTOSCAB 5% (Permethrin)
Official title: Prospective, Open-label, Multicenter, Initially Single-armed and in Case of Treatment Failure Subsequently Three-armed Randomized Clinical Trial of Phase III/IV Investigating the Escalated Therapy of Scabies With INFECTOSCAB 5% (Permethrin)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Scabies
Lead sponsor: Infectopharm Arzneimittel GmbH
Sponsor class: INDUSTRY
Collaborators: name: Winicker Norimed GmbH
First posted: 2021-03-24
Enrollment: 183
Sex: ALL
Minimum age (years): 6
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The ETSKABI study is a prospective, open-label, multicenter, initially single-armed and in case of treatment failure subsequently three-armed randomized clinical trial. Within the initial treatment phase, the to-date clinical efficacy of the standard therapy regimen according to the current German "S1-guideline for the diagnosis and treatment of scabies" is to be examined. The subsequent second phase focusses on three differently escalated treatment regimens in order to evaluate their potential to cure those patients still suffering from Scabies after standard therapy.

In total, 183 patients with Scabies who meet all inclusion criteria and do not meet none of the exclusion criteria are to be enrolled and topically treated with Permethrin 5 % cream (up to two administrations, i.e. repeated one-time on day 14 in case of persisting Scabies). In case of treatment failure by the end of phase one, adult patients will be randomized to either receive an (i) escalated therapy with Permethrin 5 % cream (repeated topical administration on two consecutive days), (ii) an add-on-combination consisting of escalated therapy with Permethrin 5 % cream and Ivermectin p.o. or (iii) an escalated therapy with Permethrin 10 % cream (up to two administrations, i.e. repeated one-time on day 14 in case of persisting Scabies).

The primary objective of the ETSKABI study is the clinical efficacy of the standard therapy by the end of phase one (standard therapy according to the S1-guideline). Beside this, clinical efficacy by the end of phase two (escalation phase) will be evaluated as well as adverse events in order to investigate over-all clinical safety.


Eligibility criteria: Inclusion Criteria:

* Confirmed acute scabies disease: detection of mites and/or mite nymphs and/or mite larvae at scabies-typical predilection sites, detected by reflected light microscopy (dermatoscopy) or light microscopy of skin samples.
* Age between 6 and 85 years
* Written informed consent of the study participant (if of age) or of all guardians (in the case of study participants who are minors \< 12 years of age) or of all guardians and the study participant (in the case of study participants who are minors ≥ 12 years of age).

Exclusion Criteria:

* Previous treatment with antiscabiosa in the last 14 days.
* Known intolerance to permethrin, other pyrethroids, chrysanthemum, ivermectin or any of the other ingredients of the study medication.
* Scabies crustosa
* Impetiginisation/eczematisation requiring in-patient treatment
* Body weight \> 120 kg
* Pregnancy, lactation
* Immunodeficiency (of any kind, including extensive local therapy (\>20% body surface area) with corticosteroids \>2 weeks in the last 4 weeks or ≥ 10 mg prednisolone equivalent \>7 days in the last 4 weeks- even without signs of scabies crustosa)
* Other serious illnesses which, in the opinion of the investigator, prevent the patient from participating in the study (including risk factors for severe COVID-19 disease in the case of SARS-CoV-2 infection).
* Planned systemic use of corticosteroids
* Planned or previous (last 4 weeks) use of systemic or cutaneous non-steroidal immunosuppressants
* Known or clinically suspected blood-brain barrier disruption (e.g. ABCB-1 (=MDR-1) mutation), and history of neurotoxic effects from ivermectin or other substrates/inhibitors of para-glycoprotein (P-gp)
* Apparent unreliability or unwillingness to cooperate.
* Inability to understand and comply with study instructions
* Known alcohol, medication or drug dependence
* Court/agency-ordered institutionalisation
* Dependence on sponsor or investigator
* Previous participation in a clinical trial within the last 30 days or in the same clinical trial

Primary outcomes:
measure: Efficacy (Yes/No)
timeFrame: day 0 - day 28
Secondary outcomes:
measure: Efficacy (treatment success) for VS1 and VS2, as well as for the corresponding follow-up visits FUS1 and FUS2 (separately and cumulatively).
timeFrame: day 14 - day 70
measure: Efficacy (therapy success) for VE5, VE101/2 (separately and cumulatively) and VEK as well as for the corresponding follow-up visits FUE5/E10/EK, separately as well as cumulatively according to visit type (regular visit, FU visit)
timeFrame: day 28 - day 70
measure: Cumulative efficacy (treatment success) of permethrin-only treatment (i.e. without combined escalation permethrin + ivermectin) by visit type (regular visit, FU visit)
timeFrame: day 28 - day 56
measure: Frequency of required repeated standard therapy as well as escalated therapy.
timeFrame: day 0 - day 70
measure: Itch (numerical rating scale (NRS) of 0-10) and change in itch vs baseline (scale differences) for all visits, for standard therapy and escalated therapy, and for escalated therapy additionally the change in itch vs start of escalated therapy.
timeFrame: day 0 - day 70
measure: Number and type of body regions affected (wrists/hands, arm pouches, armpits, genital region, groin, knee, feet/ankles/lower legs, head, torso, other) for all visits.
timeFrame: day 0 - day 70
measure: Proportion of patients (in %) with evidence of mites (incl. nymphs and larvae, reflecting light microscopy (dermatoscope) or light microscopy of skin samples) for all visits, for standard therapy and escalated therapy
timeFrame: day 0 - day 70
measure: Proportion of patients with use of antiscabiosa not conforming to study procedures for all visits, for standard therapy and escalated therapy
timeFrame: day 0 - day 70
measure: Proportion of patients with new scabies efflorescences for all treatment cycles and control visits
timeFrame: day 0 - day 70
measure: Patients with "additionally confirmed" therapy failure (in %)
timeFrame: day 0 - day 70
measure: Patients with reinfestation (in %): Proportion of patients with microscopically confirmed new efflorescences at the end of standard therapy or escalated therapy (respective FU-visit) who were assessed as cured at the immediately preceding control visit.
timeFrame: day 0 - day 70
measure: Adverse events, serious adverse events, unexpected drug reactions, serious unexpected drug reactions (total frequency, type, severity, causality, with frequencies, with separate presentation of local reactions).
timeFrame: day 0 - day 70
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Dresden
country: Germany
facility: Städtisches Klinikum Dresden
city: Halle (Saale)
country: Germany
facility: Universitätsklinik und Poliklinik für Dermatologie und Venerologie
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
Study officials:
affiliation: Universitätsklinik und Poliklinik für Dermatologie und Venerologie
name: Cord Sunderkötter, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: