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Severe Erythema Multiforme - CORTICO

ConditionErythema Multiforme
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age15+
SponsorAssistance Publique - Hôpitaux de Paris

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 15 years old and 30 kg ≤ Weight ≤ 150 kg

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Prednisone 20 Mg

    Drug

    Oral corticosteriods

  • Oral Placebo

    Drug

    Oral placebo

  • Methylprednisolone 120 Mg

    Drug

    IV corticosteriods

  • IV Placebo

    Drug

    IV placebo

Treatment groups

96 Participants
are divided into 2 treatment groups
Group A: Systemic CorticosteroidsExperimental treatment 2 interventions
Group B: PlaceboPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

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).

Time frame
Day0 to Month1
2

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.

Time frame
Day0 to Month1
3

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.

Time frame
Day0 to Month1
4

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.

Time frame
From Day 0 until discharge from hospital, assessed up to Day 15

Secondary outcomes

1

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

Time frame
Day15 and Month1
2

Time to fever resolution

fever resolution defined as absence of fever (temperature ≤ 37,8°C) for at least 24 h

Time frame
From Day 0 until discharge from hospital, assessed up to Day 15
3

Length of hospital stay

Time frame
From Day 0 until discharge from hospital, assessed up to Day 15
4

Number of days of consumption of level III analgesics

at least once in the day

Time frame
From Day 0 until complete healing, assessed up to Month 1

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Assistance Publique - Hôpitaux de Paris

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: