Severe Erythema Multiforme - CORTICO

Erythema Multiforme Clinical Trial

— SEMCORTICO  

Official title:

Severe Erythema Multiforme: A Randomized Controlled Trial Comparing a Short Systemic Corticosteroids Regimen to Placebo in the Acute Established Phase

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06266221
• Other study ID #: APHP200073
• Secondary ID: 2022-000712-59
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 1, 2024
• Est. completion date: November 1, 2027

Study information

• Verified date: February 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Saskia Oro, PhD
• Phone: 01 49 81 25 01
• Email: saskia.oro[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Erythema multiforme (EM) is an acute and often recurrent mucocutaneous disease. EM is considered a hypersensitivity immune-mediated reaction. The two main known triggering factors are Herpes simplex virus (HSV) and Mycoplasma pneumoniae (MP) infections. Typical target skin lesions characterize EM, especially oral MMs. EM is in fact mainly linked to the oral MM involvement, including intense mucosal pain, impaired food intake, weight loss, hospitalization and potential risk of fibrotic sequelae (oral, ocular, genital, oesophageal, respiratory tract) and recurrences.

The objectives of treatment for severe EM in the acute phase are to reduce the duration of lesions, prevent complications and mucosal sequelae. However, despite the lack of evidence and consensus some medical teams often use a short regimen of SCS hoping to obtain a quicker improvement of the condition. However, the use of SCS at the acute phase is not codified and remains debated according to the existent literature. Current studies are mostly retrospective and based on small cohorts or case reports. A randomized, controlled trial would be therefore essential to properly evaluate the benefit of SCS in this pathology and provide strong support to clinicians in their decision making in severe EM during the acute phase.

This research will be a Phase III randomized, multicentric, double-blind, controlled trial with two parallel groups. The efficacy of prednisone, oral at 1 mg/kg/day for 3 days, tapered to 0.75 mg/kg/day for 3 days, 0.50 mg/kg/day for 3 days, 0.25 mg/kg/day for 3 days is compared to that of placebo, oral for 12 days or IV methylprednisolone if oral route is impossible because of the self-reported inability for the patient to swallow due to the impacts of the oral lesions, with dosage equivalence at 0.8 mg/kg/day for 3 days, tapered to 0.6 mg/kg/day for 3 days, 0.4 mg/kg/day for 3 days, 0.2 mg/kg/day for 3 days, then stopped, compared to that of placebo.

A stratification according to the food intake classification (0,1,2 vs 3) will be performed.

An interim analysis is planned after the inclusion of 50 patients. Results of the interim analysis will be presented to the DSMB. During the interim analysis, inclusions may continue.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 96
• Est. completion date: November 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Age = 15 years old and 30 kg = Weight = 150 kg

• Clinical diagnosis of severe EM defined as:

• Typical skin lesions if first flare of EM: raised target lesions with 2 or 3 concentric rings located on the extremities or disseminated. In case of recurrent EM, with proven anterior flare (known clinical diagnosis as-sociating typical skin lesions and MM involvement in a previous flare), typical skin lesions are not essential for inclusion, because EM may manifest as isolated mucosal involvement.

• Two or more MMs affected (mouth, throat, eyes, ear, nose, genital and/or anal areas), or only the oral MM affected, if severely affected (score* 2 or 3 of Harman criteria22) with altered general conditions and significant impact on food intake (solid food impossible)

• First flare of EM or acute recurrence of previously diagnosed EM

• Disease flare that has lasted for up to 5 days (=5 days)

• Affiliated to a social security scheme

• Able to provide written informed consent; consent of both parents will be col-lected for minors

• score: 1, minor activity (up to three erosions); 2, moderate activity (more than three but less than 10 erosions, or generalized desquamative gingivitis); 3, severe (more than 10 discrete erosions or extensive, confluent erosions, or generalized desquamative gingivi-tis with discrete erosions at other oral sites).

Exclusion Criteria:

• EM without involvement of oral cavity compromising normal solid food

• Patients unable to eat solid food outside of their current pathology (erythema multiforme)

• Other diagnosis potentially involving MMs: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), pemphigus, herpetic gingivostomatitis

• Systemic Corticosteroids prescribed for another disease on inclusion day (any dose)

• Use of systemic Corticosteroids for > 5 days for any previous flare of EM (>10mg),

• Contraindication to systemic Corticosteroids:

• hypersensitivity to systemic Corticosteroids or to an excipient;

• uncontrolled primary bacterial, viral, fungal or parasitic infection

• psychotic states not yet controlled by treatment

• Sepsis (shock, cyanosis, hypothermia, low blood pressure monitored succes-sively twice (systemic blood pressure < 90 mmHg and diastolic blood pres-sure < 60 mmHg)

• Kidney or liver insufficiency (creatinine level = 150 µmol/L; aspartate ami-notransferase or alanine aminotransferase level > 3 times the upper limit of normal)

• Current cancer with the exception of non-metastatic skin carcinoma not re-quiring immediate medical treatment

• Pregnant or breastfeeding

• Person subject to safeguards of justice

• Person deprived of liberty by judicial or administrative decision

• Person subject to psychiatric care without their consent

• Person admitted to a health or social establishment for purposes other than those of research

• Person unable to express their consent

• Person under legal protection (guardianship or curatorship)

• Participation in another interventional study involving human participants or in the exclusion period at the end of a previous study involving human partici-pants, if applicable

• On state medical aid

Related Conditions & MeSH terms

• Erythema
• Erythema Multiforme

Intervention

Drug:
• Prednisone 20 Mg
Oral corticosteriods
• Oral Placebo
Oral placebo
• Methylprednisolone 120 Mg
IV corticosteriods
• IV Placebo
IV placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to success	It will be defined by controlled pain (Numeric Rating Scale (NR, range 0-10) score <4 and sustained no need for any level III analgesics, during 48 hours), resumption of non-blended food intake and no need for rescue therapy (IV methylprednisolone at 1mg/kg/day with discontinuation of the current treatment in both arms).	Day0 to Month1
Primary	Evaluation of Pain	It will be evaluated daily by using the NR (0-10), 3 times a day during hospitalization and once a day (worst score of the day) after the hospitalization by phone until achievement of the primary end-point. To avoid confounding bias, management of pain will be standardized: Level I, II and III analgesics will be permitted during the treatment, but analgesics taken will be reported and the success is defined as no need for any level III analgesics.	Day0 to Month1
Primary	Food intake	It will be evaluated qualitatively daily by the investigator team (eg. investigator or collaborator, dietician, trained clinical study technician) by use of a standardized questionnaire. Food intake will be classified as the following categories: 0, impossible to eat; 1, liquid food possible; 2, mixed food possible; 3, chopped food possible; 4, solid food possible. For patient with categories 0, 1 or 2 at baseline, the success will be defined by the resump-tion of categories 3 or 4. For patients with category 3 at baseline, the success will be catego-ry 4.; A subgroup analysis will be performed considering the two food intake classification strata.	Day0 to Month1
Primary	Rescue therapy intake	The rescue therapy will be standardized for all patients in failure of the initial strategy and will be: IV methylprednisolone at 1 mg/kg/day with discontinuation of the current treatment in both arms.	From Day 0 until discharge from hospital, assessed up to Day 15
Secondary	Time to clear or almost clear healing of all sites	"clear" is defined as no erosion or skin ulceration and absence of new lesions and "almost clear" is defined as "presence of 1, or 2 maximum, micro erosions / punctiform millimetric erosions, and absence of new lesions". Healing will be evaluated by the clinician. To avoid bias, the investigators will be trained before the start of the study allowing a standardization of the evaluation of healing	Day15 and Month1
Secondary	Time to fever resolution	fever resolution defined as absence of fever (temperature = 37,8°C) for at least 24 h	From Day 0 until discharge from hospital, assessed up to Day 15
Secondary	Length of hospital stay		From Day 0 until discharge from hospital, assessed up to Day 15
Secondary	Number of days of consumption of level III analgesics	at least once in the day	From Day 0 until complete healing, assessed up to Month 1
Secondary	Evaluation of pain	It will be assessed three times a day during hospitalization and once a day (worst score of the day) after the hospitalization until achievement of the primary endpoint.	From Day 0 until complete healing, assessed up to Month 1
Secondary	Chopped or solid food intake resumption		From Day 0 until complete healing, assessed up to Month
Secondary	Rate of patients in the two groups with need for a rescue therapy	The rescue therapy will be standardized for all patients in failure of the initial strategy and will be: IV methylprednisolone at 1 mg/kg/day with discontinuation of the current treatment in both arms.	From Day 0 until discharge from hospital, assessed up to Day 15
Secondary	Rate of sequelae	cutaneous and mucosal sequelae (ocular, ENT, esophageal, pulmonary and genital sequelae)), assessed clinically at month 3 (M3, if realized) and month 6 (M6)	Month3 and Month6
Secondary	Rate of adverse events during the treatment and follow-up		Day0 to Month6
Secondary	Evaluation of the quality of life	It will be performed with the use of Patient Global Impression of Change (PGIC), scale on 7 points	at the end of hospitalization, Day7, Day15 and Month1 and in case of relapse