A comparative multicentric non inferiority clinical trial of WHO MBMDT with a new monthly chemotherapy regime containing Rifampicin, Moxifloxacin and Clarithromycin (RMC) on Multibacillary patients from India.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 280
- 试验地点
- 4
- 主要终点
- Primary efficacy outcomes:
研究概览
简要总结
1. Current WHOMDT does not kill 100% bacteria even after a full course of treatment in a subset of patients harbouring a large bacterial load thus continuing transmission of the disease responsible for endemicity in some countries. The duration of MDT is long and promotes noncompliance. MDT continues to be controversial with limited evidence support resulting in multiple reformulations since the last 40 years. This calls for a search for newer, more efficacious drugs with shorter duration of action evidenced with well-designed clinical trials.
**2.**Novelty: Relapse, advocated as the key outcome measure of efficacy of MDT, has its drawbacks. Relapse studies require long years of follow up. The gold standard test for viability was Mouse foot pad studies which is costly and time consuming. Hence, we propose Molecular Viability Assays as outcome measure of efficacy which are newer and better techniques to test viability faster.
**3.**Objectives:
To determine the efficacy of monthly regimen of Rifampicin, Moxifloxacin and Clarithromycin (RMC) regimen as compared to WHO MBMDT regarding clinical cure, lab parameters, immunological reactions, Viability assays, Mouse Foot pad studies and acceptability to the patient in Multibacillary leprosy patients.
Methods:
It is an open label randomized clinical control trial where in the intervention group monthly supervised regimen of Rifampicin, Moxifloxacin and Clarithromycin will be administered in doses of 600 mg, 400 mg, and 1000 mg respectively and the control arm would be given routine WHO MB MDT. The duration of the treatment in both arms will be 12 months. The random sequence will be generated centrally which will be sent to study centres in opaque envelopes. After consent approved, the envelope will be opened, and patient put on respective arms. The study population will include newly diagnosed, previously untreated MB leprosy patients. Written informed consent will be sought from every subject included in the study.
SSS of all the study subjects will be collected at 0-day, 6th, 12th, and 24th month and transported in RNAlater to the SBL. Real Time PCR will be done to quantitate copy numbers of the genes encoding 16S rRNA, hsp18 and esxA specific for M. leprae. Resistance studies will be carried out at 12 months in patients harbouring viable bacilli. Validation of M. leprae growth in mouse foot pad will be performed on participants showing viable load by molecular method at the time of RFT in Schieffelin Institute of Health – Research and Leprosy Centre Karigiri (SIHR&LC), Vellore.
Expected outcome:
Primary efficacy outcomes:
1. Molecular
I. Reduction of copy numbers by MVA
II. Complete killing of M. leprae as demonstrated in MFP.
2. Clinical
I. Complete clinical cure, defined as full regression of the lesions.
II. Clinical improvement of the lesions defined by a clinical criterion
3. Pathological
I. Bacillary index (BI) improvement
Secondary Efficacy outcomes include:
1. Immunological outcomes
i. Neuritis - if participants reported pain during the interview or when Nerve function impairment is detected on routine test.
ii. Type I reaction
iii. Type 2 reaction
2. Safety outcomes
i. Severe side effects (defined as a side effect that forced the patient to stop the treatment),
ii. mild to moderate side effects.
3. Qualitative outcomes
i. Impact of leprosy treatment on life
ii. Perspective towards leprosy treatment
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 15.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Multibacillary (MB) leprosy, defined as 5 or more skin lesions or extensive infiltration and /or diffuse skin involvement, classified as borderline tuberculoid, borderline lepromatous or polar lepromatous, as determined using Ridley and Jopling classification system.
排除标准
- •1.History of intolerance to one of the medications.
- •2.Patients who are not able to come to the clinic every month during their treatment and during follow up.
- •3.Patients who do not give informed consent or are not capable to give informed consent due to mental impairment.
- •4.Immunocompromised patients diagnosed with HIV/AIDS and Tuberculosis.
结局指标
主要结局
Primary efficacy outcomes:
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
1. Molecular
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
- Reduction of copy numbers by MVA
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
- Complete killing of M. leprae as demonstrated in MFP.
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
2. Clinical
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
- Complete clinical cure, defined as full regression of the lesions.
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
- Clinical improvement of the lesions defined by a clinical criterion
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
3. Pathological
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
- Bacillary index (Bl) improvement
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
- Improved biopsy findings
时间窗: 1.Reduction of copy numbers by MVA - baseline , 6 months and 12 months | Complete killing of M. leprae as demonstrated in MFP - 24 months | Complete clinical cure, defined as full regression of the lesions - 6 months and 12 months | Clinical improvement of the lesions defined by a clinical criterion - 12 months | -Bacillary index (Bl) improvement - 3 , 6 and 12 months | - Improved biopsy findings - 12 months
次要结局
- 1. Immunological outcomes(- Neuritis -if participants reported pain during the interview or when Nerve function impairment is detected on routine test.)
研究者
Joydeepa Darlong
The leprosy mission trust India