A Multicentric Randomized Double-Blind Phase 3 Trial Evaluating the Efficacy of an Adapted Antibiotherapy in Hurley Stage 2 Active Hidradenitis Suppurativa Patients Versus Tetracycline Derivative
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 92
- 试验地点
- 4
- 主要终点
- Percentage of patients reaching clinical remission at week 12, defined by an improvement of 90% of the IHS4 score from the baseline (IHS4 (1))
研究概览
简要总结
The study evaluates the efficacy of an adapted antibiotherapy in Hurley stage 2 active Hidradenitis Suppurativa patients versus tetracycline derivative
详细描述
The antibiotic strategy is targeted against specific pathobionts which have been identified in HS lesions by the investigator's team.
Half of participants will receive a 3-week course of ceftriaxone + metronidazole treatment followed by 3 weeks of rifampicin + moxifloxacin + metronidazole combination, then 6 weeks of rifampin + moxifloxacin (experimental groupe), versus a 12 weeks course of lymecycline (control group) Double blind treatment phase will stop at week 12. All patients whatever their randomization arm or their remission status will begin follow-up treatment according to standard care recommendations (Société Française de Dermatologie): lymecycline, doxycycline or cotrimoxazole. Prescription will be upon decision of the investigator.
This maintenance treatment is not experimental.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults < 60 years old
- •Diagnosis of HS according to European Dermatology guidelines:
- •Recurrent inflammation occurring more than 2 times in the past 6 months in the inverse regions of the body, presenting with nodules, sinus-tracts and/or scarring.
- •Signs: Involvement of axilla, genitofemoral area, perineum, gluteal area (and infra-mammary areafor women). Presence of nodules (inflamed or noninflamed), sinus tracts (inflamed or noninflamed), abscesses, scarring (atrophic, mesh-like, red, hypertrophic or linear)
- •Active HS with i) ≥ 1 year of evolution and ii) ≥ 4 flares during the previous year
- •Clinical severity of HS at inclusion: Hurley stage 2
- •BMI < 35
- •Written informed consent from patient
- •Patient able to complete DLQI
- •Patients affiliated to the French health system (Assurance Maladie), except French state medical aid beneficiaries (Aide Médicale d'Etat)
- •Active compatible contraception for men and women of childbearing or inability to procreate
- •Available laboratory blood test performed within the last 2-months
- •Non inclusion Criteria:
- •Person < 18 and ≥ 60 years old
- •Former stage 3 HS
- •Previous use of the experimental treatment
- •Unauthorized drugs for the study during the month preceding the inclusion
- •Any contra-indication to study treatments or excipient (e.g. lactose, cornstarch, riboflavin notably):
- •pregnancy, breastfeeding, known allergy to experimental or reference drugs, wheat allergy, tendinopathy, QT prolongation, bradycardia, heart failure, heart rhythm disturbances, hydroelectrolytic disorders, hypokalemia, coagulation disorders, severe liver/kidney dysfunction, porphyria, mandatory use of nonsteroidal anti-inflammatory drugs (NSAIDs) for other medical conditions
- •Unbalanced diabetes (ie HbA1c above 7%)
- •Dysphagia, untreated gastro-oesophageal reflux/ulcer
- •Immune suppression, inflammatory disease, including gastroenterologic and rheumatologic inflammatory conditions
- •Lactase deficiency, lactose and galactose intolerance
- •Malabsorption syndrome
- •Person living in the same household as another patient
- •Person under guardianship or curatorship
- •Individuals with any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives (e.g patient unable to complete DLQI, or poor predictable observance
- •Participation in another interventional research on health products studies
- •Patients requiring repeated (more than 3/year) use of antibiotics for a chronic disease other than HS
- •Alcohol-dependant patients defined as an addiction to alcohol with a negative impact on health, social or personal life
- •Exclusion criteria:
- •Pregnancy QT prolongation Abnormal result of routine lab tests corresponding to contra-indication to study treatments Unauthorized drug for the study during all the study (from study treatments interactions listed in the SmPC, Cf. unauthorized drug listed in non-inclusion criteria).
- •Development of hypersensitivity to any of the study products and/or excipients (e.g. lactose, corn starch, riboflavin).
排除标准
- 未提供
研究组 & 干预措施
Experimental treatment
a 3-week course of ceftriaxone (Rocephin) IV injection (daily dose 2g/day)
- oral metronidazole (daily dose 1500mg) followed by a 3-week course of oral rifampicin (Rifadin with 10mg/kg/day) + moxifloxacin (Izilox daily dose 400mg) + metronidazole (daily dose 1500mg) followed by a 6-week course of oral rifampicin (Rifadin with 10mg/kg/day) + moxifloxacin (Izilox daily dose 400mg).
A placebo for lymecycline will also be administered during this intensive treatment phase
干预措施: ROCEPHIN, metronidazole, RIFADIN, IZILOX, placebo combination therapy (Drug)
Control
12-week course of oral lymecycline (Tetralysal daily dose 452mg) Placebos for all experimental drugs will also be administered during this intensive treatment phase
干预措施: Lymecyclin and corresponding placebos of the experimental arm (Drug)
结局指标
主要结局
Percentage of patients reaching clinical remission at week 12, defined by an improvement of 90% of the IHS4 score from the baseline (IHS4 (1))
时间窗: at week 12
The clinical remission is defined as a 90% improvement of the International Hidradenitis Suppurativa Severity Score (IHS4) at week 12 compared to the baseline. The IHS4 score is a validated composite score developped to assess dynamically HS severity (1). It is calculated by adding the number of inflammatory nodules to the number of abscesses multiplied by 2 and to the number of draining tunnels multiplied by 4. A total score of 3 or less corresponds to mild severity HS, 4-10 to moderate severity HS and 11 or higher to severe disease.
次要结局
- Change in Physician Global Assessment (PGA)(from baseline to week 52)
- Change in Modified Sartorius score(from baseline to week 52)
- Change in Hurley Score(from baseline to week 52)
- Change in Dermatology Life Quality Index (DLQI) score (Patient's HS evaluation)(from baseline to week 52)
- Change in Hidradenitis Suppurativa Severity Score (IHS4) score(from baseline to week 52)
- Change in Hidradenitis Suppurativa Clinical Response (HiSCR) score(from baseline to week 52)
- Change of patient pain(from baseline to week 52)
- Abnormal biological value of Hemoglobin(from baseline to week 12)
- Number of pain killers received by patients(from baseline to week 52)
- Microbiological bacterial Change on the worst lesion microbiome at W12(at baseline and week 12)
- Microbiological metagenomics Change on the worst lesion microbiome at W12(at baseline and week 12)
- Number of antibiotic treatments received by patients(from baseline to week 52)
- Time without flare of HS(from baseline to week 52)
- Change in BMI(from baseline to week 52)
- Abnormal biological value of white cells(from baseline to week 12)
- Number of adverse events of all kind(from baseline to week 52)
- Abnormal biological value of neutrophils(from baseline to week 12)
- Abnormal biological value of platelet count(from baseline to week 12)
- Abnormal value of AST liver enzyme(from baseline to week 12)
- Abnormal value of ALT liver enzyme(from baseline to week 12)
- Non complete drug administration(from baseline to week 12)