A Double-blind double dummy prospective randomized study to evaluate the efficacy of classical Ayurveda management versus Methotrexate in Rheumatoid Arthritis (AMRA Study).
试验速览
- 阶段
- 3 期
- 状态
- Other
- 发起方
- 入组人数
- 240
- 试验地点
- 3
- 主要终点
- Disease activity score (DAS 28-C-Reactive protein CRP),The American college Of Rheumatology Response criteria 20%,50%,70%(ACR 20/50/70)ACR
研究概览
简要总结
This Phase III clinical trial uses a randomized, placebo-controlled, double blind, double-dummy design to compare classical Ayurvedic outpatient treatment to the allopathic standard of care treatment (methotrexate) for rheumatoid arthritis (RA). At three centers, 218 subjects with active RA will be randomized into two groups of 109 subjects each to receive either: (1) methotrexate plus Ayurvedic placebo or (2) classic Ayurveda plus methotrexate placebo. Treatment duration will be 36 weeks; recruitment will be spread equally across the three centers.
Primary Objective: To compare DAS28-CRP responses among RA patients treated with Ayurvedic therapy or methotrexate.
Secondary Objectives:
- To compare the two groups in terms of:
a) ACR20/50/70) responses and its components
b) RA remission as defined by DAS28-CRP and CDAI criteria
c) Immunological response to Ayurvedic treatment by examining generalized measures of inflammation and cytokine response at selected points during the study
- To compare the adverse effects among patients treated with classical Ayurveda vs. methotrexate.
Exploratory Objective: To demonstrate the sensitivity to change of DAS28-CRP and HAQ-DI; and Quality of Life questionnaires in the Indian population.
Study Timeline:
Total number of months = 24
Duration of subject participation: 9 months
Data cleaning and analysis: 6 months.
Protocol
- Once every four weeks: Study visits; CBC, Chemistry, and urinalysis; dispensation of Medicine/placebo.
- Once every 12 weeks: Full rheumatologic evaluations
Safety: Hematology, chemistry battery, and urinalysis; open-ended questions on adverse events; Medical Safety Officer (unblinded); Ayurvedic medicines tested for heavy metal and microbial content; Data Safety Monitoring Board.
Randomization will be done by the Central Study Pharmacist, using random permuted block design with varying block sizes implemented on a Web-based data management system by the Study Statistician. Once a patient is determined to be eligible, based on definitive inclusion and exclusion criteria, the patient can be randomized at the Baseline visit.
The Study Pharmacy at each center will be responsible for proper preparation and dispensing of the study medication and placebo within the randomization protocol.
Blinding: Only the Central Study Pharmacist, who will be a specialist in Ayurvedic pharmacology, will be the only unblinded person for the entire duration of the trial.
When changes in medication are made in the Ayurvedic treatment group, corresponding changes will be made to the prescriptions in the methotrexate group which would be receiving Ayurvedic placebo, so that unblinding will not occur during the course of the study. All subjects, regardless of treatment group, will receive the same amount of attention and have the same assessments done at each visit. Both Ayurvedic physician and allopathic physician will see subjects at each visit.
Statistical Analysis (will be described fully before the start of the study)
- Descriptive analysis
- ANOVA or ANCOVA for parametrically distributed data
- Chi-Square or Wilcoxon Test for non-parametric data
- Adverse events described and tested as appropriate
- Exploratory endpoints tested as appropriate
- Ancillary analyses including Success of double-blinding; Compliance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Adult male or female aged between 18 and 65 years, inclusive.
- •Expected to survive more than or equal to 2 years from their inclusion in the protocol.
- •Able to give informed consent and able to read and/or understand instructions in English, Tamil, Malayalam, Kannada, Hindi, Marathi.
- •Rheumatoid Factor positivity or Anti-CCP positivity.
- •Active disease as defined by fulfillment of the following criteria at 2 visits that are at the most four weeks apart (i.e., at screening and baseline visits): At least 9 of 68 joints assessed as painful or tender on motion.
- •Functional RA classes I, II, or III according to the 1991 ACR classification criteria.
- •Functional RA class IV patients will be permitted if they are not wheelchair or bed bound.
排除标准
- •History of an acute inflammatory joint disease as defined by ACR/EULAR criteria other than RA which might interfere with the evaluation of the patient’s RA in this study (e.g., SLE, dermatomyositis/polymyositis,reactive arthritis, ankylosing spondylosis, vasculitis).
- •Significant symptomatic osteoarthritis.
- •Acute major trauma to joints within 1 year of study entry such that the joint is fused or non-functional.
- •Previous classic, complete Ayurvedic treatment for RA in the past 6 months, or have used OTC Ayurveda products within 1 month of entry into the study.
- •Currently enrolled in another clinical trial or received an investigational drug within 3 months(or 5 halflives, whichever is longer) prior to entry in the study.
- •Treatment with intra-articular corticosteroid injections in joint within 4 weeks of study entry.
- •Treatment with leflunomide (Arava) within 4 months before intake into study.
- •Previous treatment with methotrexate (greater than 4 doses).
- •Treatment with biologic or targeted synthetic DMARDS within the periods listed below before their baseline visit.
- •Treatment with any immunosuppressive agent (e.g., Azathioprine, Cyclosporine, etc.) within one month of study entry.
- •Chronic infections or a previous infection including intestinal ova and parasites requiring antimicrobial therapy within 1 month of study entry.
- •Concomitant disorders (e.g., diabetes mellitus, hypertension) which are poorly controlled.
- •Cardiac failure (stage III or IV according to the classification of the New York Heart Association, NYHA).
- •Uric acid >11mg/dL or well documented episode of gout according to ACR criteria for gout.
- •Impaired renal function, as shown by serum creatinine 1.5 times above the ULN of the laboratory.
- •Active liver disease OR previous liver disease that has not completely resolved, as shown by serum levels of alkaline phosphatase >2 times lab ULN; SGPT (ALT) >3 times the ULN of the lab; and/or a total bilirubin level less than 2.0 mg/dl
- •Active Hepatitis B or Hepatitis C positive by ELISA; HIV positive per previous screening.
- •Active Tuberculosis (TBC).
- •Can be treated and then started on study.
- •History of cancer or lymphoproliferative disease in the past 5 years.
- •White blood cell count less than 2000/ml, platelet count less than 100, 000/ml, or hemoglobin less than 8 g/L (5.27 mmol/L).
- •If WBC less than 2000/ml but PMN greater than 1000, subject may still be included.
- •Any condition that would, in the investigators opinion, compromise the subjects ability to absorb, tolerate, metabolize, or excrete the study medication or could cause unacceptable risk to the patient.
- •History of recent, clinically significant drug or alcohol abuse (eg, drug seeking behaviour which intereferes with family or work), in the past six months.
- •Mental condition rendering the subjects unable to understand the nature, scope and possible consequence of the study.
- •Subject unlikely to comply with protocol (e.g., non-compliance, inability to return for follow-up visits, and likelihood of not completing the study).
- •If the patient requires more than 3 g per day acetaminophen or whose NSAID intake is more than the maximum dose allowed in the package insert.
结局指标
主要结局
Disease activity score (DAS 28-C-Reactive protein CRP),The American college Of Rheumatology Response criteria 20%,50%,70%(ACR 20/50/70)ACR
时间窗: the Primary outcome will be assessed at 12th, 24th and 36th week. | the secondary outcome will be assessed at oth week and 36th week.
次要结局
- American College of Rheumatology Response Criteria 20%,50%, 70%(A CR20/50/70)responses and its components.(Immunological response to ayurvedic treatment and cytokine response at selected points during the study)