Pragmatic, Randomized, Multicenter, Double-blind, Controlled, Clinical Trial of Prednisolone Versus Colchicine for Acute Gout in Primary Care
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 186
- 试验地点
- 130
- 主要终点
- Most severe pain in the last 24 hours
研究概览
简要总结
Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated. Furthermore, majority of previous research studies were not only conducted in tertiary centres but also excluded patients with common comorbidities due to contraindications with naproxen.
This pragmatic, prospective, double-blind, parallel-group, randomized, non-inferiority trial will investigate whether prednisolone (treatment drug) is comparable or only acceptably worse than treatment with colchicine (comparison drug) in patients presenting with acute gout. Patients presenting with acute gout to their general practitioners in 60 practices across 3 university sites (Greifswald, Göttingen, and Würzburg) will be invited to participate. Patients often excluded by previous studies due to contraindications with naproxen will also be able to participate. The investigators will compare the absolute levels of the most severe pain on day 3 (in the last 24 hours) measured with an 11-item numerical rating scale as the primary endpoint. Day 0 is the day patients take their study medication for the first time. They are then asked to fill out a study diary at the same time each day to quantify their pain. Pain scores will then be used as comparison between the two medications.
详细描述
SCIENTIFIC BACKGROUND:
Gout is one of the most common rheumatic diseases, affecting 3-6% of men and 1-2% of women in western countries. Due to the severe pain and impaired quality of life, the individual burden of disease during an acute gout attack is very high. Currently, there are several approved medications available for the treatment of acute gout attacks. The EULAR (European League Against Rheumatism) guideline recommends colchicine as the drug of first choice for acute gout attacks. But according to it, non-steroidal anti-inflammatory drugs (NSAIDs) and systemic corticosteroids can also be used. In contrast, DEGAM (German Society for General Medicine and Family Medicine) recommends using prednisolone.
Most commonly, gout attacks are treated in general practices. However, studies on the treatment of acute gout attacks have so far been conducted mainly in specialised centres, and thus in a selective patient group. The gold standard for the diagnosis of gout in rheumatology centres is the detection of monosodium urate crystals in aspirated joint fluid. In primary care, however, the diagnosis of gout is made on the basis of clinical symptoms alone. Because of the risk of injury and infection, joint puncture is not usually performed on patients in a general practice setting.
Prednisolone and low-dose colchicine were selected for the study due to a high prevalence of patients with contraindications to NSAIDs, including, cardiovascular disease, oral anticoagulation, chronic kidney disease or a history of gastrointestinal disease. Approximately 20-30% of patients with gout are poorly suited for NSAID administration and in previous studies, those patients were excluded.
RESEARCH QUESTION:
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)
盲法说明
There are 2 active and effective treatments (colchicine vs. prednisolone). The allocation to the treatment arms is 1:1, and study participants are randomised to either group. Randomisation is intended to reduce selection and allocation bias.
As both drugs have different dosing regimens, the investigators provide identical blisters for both drugs including the active substance and corresponding placebos. This way, all study participants receive the same number of tablets and the possibility of drug prediction is more difficult. This is achieved by using tablets that are identical in taste and appearance (double-dummy design). Participants randomised to the colchicine arm will receive colchicine plus prednisolone placebo. Participants randomised to the prednisolone arm will receive prednisolone plus a colchicine placebo. The prednisolone placebos contain a bittering agent due to the bitter taste of prednisolone to ensure a similar taste.
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
- •Adult patients ≥ 18 years of age
- •Clinical diagnosis of acute attack of gout (symptoms: pain, swelling, tenderness, redness or local hyperthermia).
- •Acute pain in hand or foot (podagra, chiragra)
- •The onset of pain was no more than 2 days ago (e.g., presentation on Monday afternoon, onset of pain on Saturday morning)
- •Willingness to participate in the study and ability to give written informed consent.
排除标准
- •Known intolerance or contraindication to either medication
- •Known intolerance to the placebo (e.g. lactose intolerance).
- •Existing (or less than 2 weeks ago) oral treatment with corticosteroids or colchicine.
- •Known chronic kidney disease (CKD stage 4 or greater) or an available value of estimated glomerular filtration rate (eGFR) < 30ml/min/1.73 m².
- •Known haematopoietic disorder or available values of platelets < 30,000 µl or leucocytes < 4000 µl, or Hb <5 mmol/l/ or 8 g/dl
- •Uncontrolled high blood pressure (systolic blood pressure permanently above 160 mmHg).
- •Known liver cirrhosis or severe liver disease or available liver enzymes results (ie. Serum Glutamate Oxalate Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase(SGPT)) being elevated by more than twice the respective reference range
- •Known current gastric or duodenal ulcer (diagnosed in the last 4 weeks)
- •Current chemotherapy or chemotherapy completed less than 3 months ago
- •Known HIV infection
- •Solid organ transplant with immune suppression
- •Desire to have children within the next 6 months in both men and women
- •Existing pregnancy or breastfeeding
- •Participation in other studies according to the German Medicines Act in the last 3 months
- •Participation in the COPAGO study with past gout attack
研究组 & 干预措施
Prednisolone 30mg (Day 0-4)
As both drugs have different dosing regimens, the investigators provide identical blisters for both drugs including the active substance and corresponding placebos. This way, all study participants receive the same number of tablets and the possibility of drug prediction is more difficult. This is achieved by using tablets that are identical in taste and appearance (double-dummy design). Participants randomised to the prednisolone arm will receive prednisolone plus a colchicine placebo. The prednisolone placebos contain a bittering agent due to the bitter taste of prednisolone to ensure a similar taste.
The dosage is according to EULAR guideline and also within the recommended range of the DEGAM guideline. The cumulative total dose taken per participant within the clinical trial is 150 mg for prednisolone.
干预措施: Prednisolone 30 mg Tablet (Drug)
Colchicine 1.5 mg (Day 0), 1.0 mg (Day 1-4)
As both drugs have different dosing regimens, the investigators provide identical blisters for both drugs including the active substance and corresponding placebos. This way, all study participants receive the same number of tablets and the possibility of drug prediction is more difficult. This is achieved by using tablets that are identical in taste and appearance (double-dummy design). Participants randomised to the colchicine arm will receive colchicine plus prednisolone placebo.
The dosage is according to EULAR guideline and also within the recommended range of the DEGAM guideline. The cumulative total dose taken per participant within the clinical trial is 5.5mg for colchicine.
干预措施: Colchicine 0.5 mg Oral Tablet (Drug)
结局指标
主要结局
Most severe pain in the last 24 hours
时间窗: Day 3
To investigate whether the efficacy of prednisolone in General Practitioner's care is equally good or only marginally weaker than treatment with low-dose colchicine, the most severe pain in the last 24 hours on day 3 after baseline on an 11-point numerical rating scale is used and compared across groups. The study participants take their study medication for the first time on day 0 and are then asked to fill out their diary daily at the same time to quantify their pain. 0 stands for no pain and 10 for the strongest pain imaginable.
次要结局
- Frequency of use of non-pharmacological pain therapies(Day 1 - 6)
- Average response to treatment(Day 1, 2, 3, 4, 5, 6)
- Swelling and tenderness of the joint(Day 3)
- Physical function(Day 1 and 6)
- Patients' global assessment of treatment success(Day 6)
- Most severe pain in the last 24 hours depending on disease duration(Day 1 and 6)
- Frequency of use of additional pain medication by treatment group(Day 1 - 6)