Clinical trial NCT06266221: Severe Erythema Multiforme - CORTICO
Official title: Severe Erythema Multiforme: A Randomized Controlled Trial Comparing a Short Systemic Corticosteroids Regimen to Placebo in the Acute Established Phase
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Erythema Multiforme
Keywords: Erythema
Corticoids
Prednisone
Methylprednisolone
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-02-20
Enrollment: 96
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to success
timeFrame: Day0 to Month1
measure: Evaluation of Pain
timeFrame: Day0 to Month1
measure: Food intake
timeFrame: Day0 to Month1
measure: Rescue therapy intake
timeFrame: From Day 0 until discharge from hospital, assessed up to Day 15
Secondary outcomes:
measure: Time to clear or almost clear healing of all sites
timeFrame: Day15 and Month1
measure: Time to fever resolution
timeFrame: From Day 0 until discharge from hospital, assessed up to Day 15
measure: Length of hospital stay
timeFrame: From Day 0 until discharge from hospital, assessed up to Day 15
measure: Number of days of consumption of level III analgesics
timeFrame: From Day 0 until complete healing, assessed up to Month 1
measure: Evaluation of pain
timeFrame: From Day 0 until complete healing, assessed up to Month 1
measure: Chopped or solid food intake resumption
timeFrame: From Day 0 until complete healing, assessed up to Month
measure: Rate of patients in the two groups with need for a rescue therapy
timeFrame: From Day 0 until discharge from hospital, assessed up to Day 15
measure: Rate of sequelae
timeFrame: Month3 and Month6
measure: Rate of adverse events during the treatment and follow-up
timeFrame: Day0 to Month6
measure: Evaluation of the quality of life
timeFrame: at the end of hospitalization, Day7, Day15 and Month1 and in case of relapse
Other outcomes:
Locations:
Study officials:
affiliation: APHP
name: Candy Estevez, M.Sc
role: STUDY_CHAIR
References: