Treatment of Chronic Hand Eczema With Oral Roflumilast (HERO) - a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Proportion of patients achieving at least 75% reduction in hand eczema severity index (HECSI75) at week 16 when compared to HECSI at baseline.
研究概览
简要总结
This study is a multicentre, double-blinded, randomized, placebo-controlled, clinical trial with open-label extension.
The purpose and aim of this study is to investigate the efficacy and safety of roflumilast (PDE4-inhibitor) in adult patients with chronic hand eczema (CHE).
Patients will receive 16-week treatment with either roflumilast or placebo tablets. Hereafter, both groups continue in open-label treatment for 12 weeks where both groups will receive treatment with roflumilast.
详细描述
This study will investigate the efficacy and safety of roflumilast in adult patients with CHE and it is hypothesized that patients treated with oral roflumilast (500 microgram once daily) will experience an improvement in their moderate-to-severe CHE (measured by hand eczema severity index (HECSI)) and alter the skin microbiome. Secondly, it is hypothesized that patients treated with oral roflumilast will experience improved lung function and weight loss.
This study includes two phases:
Phase 1: 20 patients will receive 500 microgram tablet of roflumilast once daily for 16 weeks while 20 patients will receive placebo once daily for 16 weeks.
Phase 2: All 40 patients from phase 1 will receive 500 microgram tablet of roflumilast once daily for 12 weeks.
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
- Double (Participant, Investigator)
盲法说明
The investigators as well as the participating patients are blinded during the RCTs phase 1 of roflumilast/placebo. No one is blinded in phase 2 because it is an open-label extension.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Age ≤ 75 years
- •HECSI ≥ 18 (moderate to severe hand eczema)
- •IGA-CHE ≥ 3
- •Body mass index (BMI) ≥ 20 kg/m2
- •Negative pregnancy test (only women of child-bearing potential (see section 2.8))
- •Willing to use safe anticonception during entire study and at least 1 week after end of treatment (-5 times plasma half-life of Roflumilast). This only account for women child-bearing potential
- •Speaks, understands, and reads danish.
排除标准
- •Severe immunological disease, e.g. HIV, systemic lupus, and systemic sclerosis
- •Diagnosis of current tuberculosis
- •Current viral hepatitis
- •History of heart failure (NYHA III-IV)
- •History of moderate or severe liver failure (Child-Pugh B-C)
- •Current or former depression with suicidal ideation
- •Topical therapy (anti-inflammatory) for chronic hand eczema 14 days before randomization
- •Topical therapy (anti-inflammatory) for chronic hand eczema during study
- •Systemic therapy for chronic hand eczema 28 days before randomization
- •Systemic therapy for chronic hand eczema during study
- •Current treatment with oral dicloxacillin or macrolide
- •Current treatment with topical antibiotics
- •Diagnosis of contact eczema of clinical significance 3 months before randomization
- •Previous treatment with apremilast (Otezla®) or roflumilast (Daxas®)
- •Confirmed pregnancy
- •Breast feeding
- •Blood donation during study
- •Allergy to roflumilast or any other PDE-4 inhibitor
研究组 & 干预措施
Placebo
20 of the participating patients are randomized to the active arm where systemic placebo tablets are received.
干预措施: Placebo (Drug)
Roflumilast
20 of the participating patients are randomized to the active arm where systemic roflumilast 500 microgram tablets are received.
干预措施: Roflumilast 500 Mcg Oral Tablet (Drug)
结局指标
主要结局
Proportion of patients achieving at least 75% reduction in hand eczema severity index (HECSI75) at week 16 when compared to HECSI at baseline.
时间窗: Through study completion, an average of 28 weeks
HECSI is a measure of hand eczema disease severity considering the extent and intensity of the disease. Each hand is divided into five areas (fingertips, fingers (except the tips), palms, back of hands and wrists) and each area is graded on the intensity of six clinical signs: erythema, induration/papulation, vesicles, fissuring, scaling, and oedema. The grading scale used is: 0, no skin change; 1, mild disease; 2, moderate and 3, severe. The affected area for each location (total of both hands) are given a score from 0 to 4 (0, 0%; 1, 1-25%; 2, 26-50%; 3, 51-75% and 4, 76-100%) for the extent of clinical symptoms. Finally, the total sum of the intensity of the six clinical signs multiplied by the extent of each location is called HECSI score and it may vary from 0 to a maximum of 360 points, with higher scores reflecting greater disease severity. The score reflects HE severity as following: 1-16, mild HE; 17-37, moderate HE; 38-116 severe HE and 117-360, very severe HE.
次要结局
- Change from baseline in NRS - Patient treatment satisfaction within the last 7 at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in quality of life hand eczema questionnaire (QOLHEQ) at assessments.(Through study completion, an average of 28 weeks)
- Proportion of patients achieving at least 50% reduction in baseline HECSI (HECSI50) at assessments.(Through study completion, an average of 28 weeks)
- Proportion of patients achieving at least 90% reduction in baseline HECSI (HECSI90) at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in dermatology life quality index (DLQI) at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in numeric rating scale (NRS) - Peak skin pain on hands within the last 24 hours at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in NRS - sleeplessness within the last 24 hours at assessments.(Through study completion, an average of 28 weeks)
- Proportion of patients achieving at least 100% reduction in baseline HECSI (HECSI100) at assessments(Through study completion, an average of 28 weeks)
- Percent change from baseline in HECSI score at assessments.(Through study completion, an average of 28 weeks)
- Change (2 or more points) in physician global assessment for chronic hand eczema IGA-CHE) at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in patient's global assessment (PaGA) at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in NRS - sleeplessness within the last 7 at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in numeric rating scale (NRS) - Peak skin pain on hands within the last 7 days at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in NRS - Peak itch on hands within the last 24 hours at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in NRS - Peak itch on hands within the last 7 days at assessments.(Through study completion, an average of 28 weeks)
- Change from baseline in work productivity and activity impairment: CHE (WPAI:CHE) at assessments.(Through study completion, an average of 28 weeks)
- Adverse events (AEs), serious adverse events (SAEs), serious adverse reactions (SARs), and suspected unexpected serious adverse reactions (SUSARS) documented at assessments.(Through study completion, an average of 28 weeks)
研究者
Jacob Pontoppidan Thyssen
Professor, MD, DMSc
Bispebjerg Hospital