Prophylaxis of Recurrent Erysipelas in Lower Limbs: compreSsion thErapy vs aNTibiotics and Compression Therapy.

Official title

Prophylaxis of Recurrent Erysipelas in Lower Limbs: compreSsion thErapy vs aNTibiotics and Compression Therapy. A Non-inferiority, Multicentre, Randomized Clinical Trial.

Overview

Erysipelas (superficial cellulitis) is a frequent streptococcal bacterial infection. Each episode of erysipelas may worsen preexisting lymphedema and evolve to life-threatening necrotizing soft-tissue infection. Moreover, each attack of cellulitis may worsen lymphatic damage and therefore favour additional attacks. Recurrence is frequent: 10-30% of cases and even up to 50%. In this context, at least 2 episodes of erysipelas in the same limb during a 1-year period defines recurrent erysipelas requiring prophylaxis. Such prophylaxis is based usually on penicillin therapy. Compression was evaluated only in a monocentric randomized controlled trial, and was never compared to antibioprophylaxis. The investigators hypothesized that compression therapy alone might represent a single intervention for prophylaxis of erysipelas recurrence as efficient as long-term antibiotic prophylaxis with compression therapy combined. This study is a multicenter, parallel groups, assessor-blinded, non-inferiority, randomized clinical trial. Main objective is to evaluate whether supervised compression therapy alone is non-inferior to supervised compression therapy + oral penicillin in controlling relapse of recurrent erysipelas. Secondary objectives are to assess time to first recurrence ; to assess the severity of the recurrence ; to assess the safety of the intervention to assess the quality of life during the prophylaxis phase ; to assess the adherence of patients with the intervention and to assess, in a joint analysis, that supervised compression therapy is both not inferior in terms of QALY and not more expensive at 1 year than supervised compression therapy + antibiotic. The study will included male or female adults who have had at least 2 episodes of recurrent erysipelas at the same leg within the previous 52 weeks, and no more than five episodes of erysipelas in the same areas of the lower limbs during the year before randomization. Experimental group is supervised compression therapy + emollient cream during 12 months and control group is supervised compression therapy + emollient cream + oral penicillin (phénoxyméthylpénicilline) during 12 months Main outcome is the proportion of patients with at least one recurrence of erysipelas during the 1-year prophylaxis phase, performed by an assessor-blinded. Patients will be identified in a hospital setting, or referred by physicians servicing the local region, or by direct advertising through patients' associations. If the patient gives consent to participate, at the end of a inclusion visit (V0), the randomization will be performed via the e-CRF. Prescriptions will then be issued on inclusion. Control group who will start antibiotic treatment at inclusion. A run-in period of 7 ±2 days will be planned between V0 and the beginning of the compression therapy for the both group, in order to get the prescribed elastic stockings, and to train the nurse in charge of the compression supervision. A nurse trained in the study will supervise the first applications of the compression in the patient's home. After inclusion visit (V0), a home visit by the liberal IDE will be planned at M1 for to check daily adherence (use of ATB or/and wearing compression and application of emollients). A patient diary must be completed from inclusion and during the follow-up period. Two telemedicine clinic were scheduled at M3 and M9 and two study visits were scheduled at M6 and M12 with a complete physical examination. All the evaluations will be performed by a blinded evaluator investigator. Supplementary telemedicine clinic(s) in case of potential recurrence of erysipelas will be done by the blinded evaluator in the presence of the nurse who will be at bedside of patient. The organization and design of the study will be realistic, and thus is designed to facilitate its feasibility and generalizability of results. In case of demonstration of non-inferiority of supervised compression therapy, patients with recurrent erysipelas will be spared of antibiotics first-line, and therefore suppress the impact of both long-term antibiotics on gut microbiota individuals and health burden of antibiotics at the population level.

Interventions

• Device elastic stockings
  thighs-high stockings, produced by means of circular knitting, corresponding to the patient's measurements
• Drug Phenoxymethylpenicillin
  Phenoxymethylpenicillin (Oracilline) 1 Million UI twice a day, per os, during one year

Primary outcome measures

• Proportion of patients with at least one recurrence of erysipelas during the 1-year prophylaxis phase, performed by a assessor-blinded [Time frame: From enrollment to the end of treatment at 12 months]

Secondary outcome measures (9)

• Time to the first confirmed recurrence of erysipelas [Time frame: From enrollment to the first confirmed recurrence of erysipelas, e.g.up to 52 weeks]
• Severity of recurrence : erysipelas-related hospital admission (number of nights in hospital for cellulitis) [Time frame: From enrollment to the end of treatment at 12 months]
• Severity of recurrence: presence of skin necrosis or ulceration [Time frame: From enrollment to the end of treatment at 12 months]
• Assessment of adverse effects and serious adverse effects during the study [Time frame: From enrollment to the end of treatment at 12 months]
• Quality of life: Dermatology Life Quality Index (DLQI) [Time frame: Month 0, Month 3, Month 6, Month 9, Month 12 and in case of potential recurrence, e.g.up to 52 weeks]
• Quality of life: EuroQuol-5 Dimensions-5 Levels standardised questionnaire (EQ-5D-5L) [Time frame: Month 0, Month 3, Month 6, Month 9, Month12 and in case of potential recurrence]
• Adherence: number of days per week that compression was worn [Time frame: From enrollment to the end of treatment at 12 months]
• Adherence: assessment of oedema by circumferential measurements [Time frame: Month 0, Month 6, Month 12]
• Adherence: number of days per week that antibiotics is taken [Time frame: From enrollment to the end of treatment at 12 months]

Eligibility criteria

Inclusion criteria

• Male or female
• ≥ 18 years of age
• At least 2 episodes of recurrent erysipelas at the same leg within the previous 52 weeks, and no more than five episodes of erysipelas in the same areas of the lower limbs during the year before randomization
• The last recurrent erysipelas have to be diagnosed within the previous 3 months
• BMI < 40 kg/m2 (no morbid obesity)
• Able to apply the compression alone or with a helper (e.g., nurse, household member)
• Affiliated with a social security regimen
• Able to consent and written informed consent obtained from the participant
• Able to understand the aims of the study and to comply with the requirements of the study
• Able to participate and be followed up during the study period

Exclusion criteria

• Any causes of immunosuppression: known HIV+ infection, organ transplantation, bonemarrow transplantation, immunosuppressive regimens for any disease, malignancy or lymphoproliferative disorder
• Receiving antibiotic treatment for erysipelas
• Received antibiotic prophylaxis for recurrent erysipelas in the year before randomization

\_ Received short- or long-term antibiotic therapy for a condition other than erysipelas

• Already wore effective compression therapy (worn at least 5 days a week) in the 3 months before randomization
• Contraindication to compression therapy (ie heart failure, arterial occlusive disease,including obliterative peripheral arterial disease with a systolic pressure index < 0.6, advanced diabetic microangiopathy for compression > 30 mmHg, phlegmasia cerulea dolens, and septic thrombosis)
• History of known hypersensitivity to beta-lactamines or contraindications to Phenoxymethylpenicillin (Oracilline) or to any of the other components of the medicine as per its SmPC
• Contraindications to the emollient cream in accordance with its SmPC
• Diabetic foot and fractures
• Woman of childbearing potential not using a highly effective method of contraception\*, or having a desire to conceive, during the whole trial duration. A β-HCG test will be performed in all woman of childbearing potential
• Persons covered by articles L1121-5 to L1121-8 of the Code de Santé Publique (corresponding to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, minors, and persons subject to a legal protection measure: guardianship or trusteeship).
• Participation in another interventional research with an investigational drug or medical device.
• Mental state rendering the person giving consent incapable of understanding the trial;
• Patient being the investigator, or any member of the team or relative of the investigator directly involved in the trial, including assistant doctors, pharmacists, nurses, trial coordinator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

France · 25 centers

• AMIENS — Amiens
• Bordeaux-D — Bordeaux
• Bordeaux-I — Bordeaux
• TOURS-D — Chambray-lès-Tours
• CRETEIL — Créteil
• DIJON — Dijon
• GRENOBLE — La Tronche
• LE MANS — Le Mans
• … and 17 more centers

Identifiers

NCT: NCT07549594 · DR230313

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗