A Phase II Randomised Study of Oral Prednisolone in Early Diffuse Cutaneous Systemic Sclerosis (Initially Double-blind, Then Switched to Open-label Because of Covid-19)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 14
- 主要终点
- Health Assessment Questionnaire Disability Index (HAQ-DI)
研究概览
简要总结
This is a randomised placebo-controlled study of moderate dose prednisolone for 6 months in patients with early diffuse cutaneous systemic sclerosis (dcSSc). Seventy-two patients within 3 years of the onset of skin thickening will be recruited from 14 UK centres over 3 years. Co-primary end-points will be the Health Assessment Questionnaire Disability Index (HAQ-DI) and the modified Rodnan skin score (mRSS). Patients will be assessed 5 times: screening, baseline, 6 weeks, 3 and 6 months, with a code-break on exit from the study at 6 months.
Please note: From August 2020, the trial was re-started following halt due to Covid-19 as open-label. The placebo arm is the 'no treatment' arm and there is no longer a code-break at study exit.
详细描述
The study is a non-commercial phase II randomised, double-blind, placebo-controlled, multi-centre study to test moderate dose prednisolone versus placebo in patients with early diffuse cutaneous systemic sclerosis (dcSSc).
Our aim is to investigate whether treatment with the steroid prednisolone is beneficial in patients with early diffuse cutaneous systemic sclerosis (also termed "scleroderma"). This is a controversial subject. Although it is very possible that prednisolone can help relieve the severe pain, itching, and disability (due to contractures and musculoskeletal involvement) of early diffuse scleroderma, doctors are often reluctant to prescribe prednisolone because of possible side effects, particularly an increased risk of serious kidney problems. Our proposed trial, treating patients with either prednisolone or placebo therapy for 6 months, should provide clinicians with a long awaited answer to the important clinical question: Can prednisolone be used as a therapy in this group of patients?
The study, funded by Arthritis Research UK, aims to determine:
- Is moderate dose prednisolone effective in reducing pain, disability and skin thickening in patients with early diffuse scleroderma?
- Is moderate dose prednisolone a safe therapy in patients with early diffuse scleroderma (with particular reference to kidney function)?
If the answer to both is 'yes', then prednisolone therapy will be much more widely prescribed for this patient group.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blind. The trial management team are blind to treatment allocation for the duration of the trial. The site research teams and patients are blind to treatment until code-break. At this point the on-site team and patient are unblind to allocation for continuing care. The site pharmacy personnel, PRedSS trial monitor and supervising statistician are unblind throughout.
From August 2020: Open-Label - The patient, site research team and site pharmacy are unblind. The trial management team are unblind for patients recruited from August 2020 onwards but remain blind to patients randomised to trial under the double-blind design. The trial monitor and trial statistician continue to be unblind for all patients randomised to trial.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients presenting with dcSSc with skin involvement extending to the proximal limb and/or trunk.
- •Male or female age ≥ 18 years.
- •Skin involvement of less than 3 years defined by patient report or clinician opinion.
- •Patient is able and willing to follow the requirements of the study.
- •Fully written informed consent.
排除标准
- •Patients with significant uncontrolled Stage 1 Hypertension (clinic BP >140/90mmHg i.e. either >140mmHg OR >90mmHg). Patients with previous hypertension which is controlled (clinic BP <140/90mmHg) for at least 4 weeks are considered eligible.
- •Previous renal crisis or significant renal impairment (estimated Glomerular Filtration Rate (eGFR) < 40 ml/min).
- •Patients currently on steroid therapy, or previous steroid therapy within the last 4 weeks, with the exception of inhaled steroids for respiratory diseases.
- •Patients currently participating in another randomised controlled trial of an investigational agent or device, or previous participation within the last 30 days.
- •Patients currently receiving an immunosuppressant or biologic therapy the dose of which has changed in the last 4 weeks prior to the baseline visit, or is likely to change during the first 3 months of study treatment.
- •Patients with major myositis or inflammatory arthritis. Patients with low level myositis or inflammatory arthritis are eligible for inclusion (for example, in the case of myositis, a creatine kinase less than 4 times the upper limit of normal or myositis only demonstrable on magnetic resonance imaging).
- •Female patients who are pregnant at time of screening.
- •Female patients who are breastfeeding.
- •Patients with significant inflammatory bowel disease as judged by the investigator.
- •It is important that patients do not suddenly stop taking the study medication. Patients who do not fully understand this, will be excluded.
- •Patients who are unwilling or unable to provide informed consent.
研究组 & 干预措施
Prednisolone
Prednisolone 5mg enteric-coated tablets, over-encapsulated in a hard gelatine capsule and filled with lactose BP. The prednisolone will be self-administered, orally with water before or after a meal once a day. Dosing will be continuous for a total of 6 months.
The total dose prescribed will be equivalent to approximately 0.3mg/kg/day. The minimum dose prescribed will be 10mg per day (2 capsules) and a maximum of 30mg per day (6 capsules).
From August 2020: The prednisolone is no longer over-encapsulated. Prednisolone 5mg enteric-coated tablets will be prescribed and taken as above.
干预措施: Prednisolone 5 mg (Drug)
Placebo oral capsule; From August 2020 - 'no additional treatment'
The placebo will be a hard gelatine capsule filled with lactose BP and identically matched to the prednisolone capsules. The placebo will be self-administered once a day, orally with water before or after a meal. Dosing will be continuous for a total of 6 months.
From August 2020 - no placebo capsule will be administered.
干预措施: Placebo oral capsule; From August 2020 'no additional treatment' (Drug)
结局指标
主要结局
Health Assessment Questionnaire Disability Index (HAQ-DI)
时间窗: Baseline to 3 months
The mean difference in HAQ-DI at 3 months
modified Rodnan Skin Score (mRSS)
时间窗: Baseline to 3 months
The difference in mRSS at 3 months
次要结局
- Health related quality of life - Assessed by Questionnaire(Baseline to 6 weeks, 3 months and 6 months)
- Pain and disability - Assessed by Questionnaire(Baseline to 6 weeks, 3 months and 6 months)
- Fatigue - Assessed by Questionnaire(Baseline to 6 weeks, 3 months and 6 months)
- Health related quality of Life - Assessed by Questionnaire(Baseline to 6 weeks, 3 months and 6 months)
- Hand function - Assessed by Questionnaire(Baseline to 6 weeks, 3 months and 6 months)
- Assessment of pain - Clinician assessment(Baseline to 6 weeks, 3 months and 6 months)
- Quality of life and functional ability - Assessed by Questionnaire(Baseline to 6 weeks and 6 months)
- Functional ability - Assessed by Questionnaire(Baseline to 6 weeks, 3 months and 6 months)
- Pain associated with itch - Assessed by Questionnaire(Baseline to 6 weeks, 3 months and 6 months)
- Pain and disability(Baseline to 6 weeks, 3 months and 6 months)
- Anxiety and depression - Assessed by questionnaire(Baseline to 6 weeks, 3 months and 6 months)
研究者
Prof. Ariane herrick
Professor of Rheumatology
University of Manchester