Clinical trial of WHO multibacillary multidrug therapy versus rifampicin, moxifloxacin and clarithromycin on multibacillary leprosy patients from India

ISRCTN	ISRCTN70846313
DOI	https://doi.org/10.1186/ISRCTN70846313
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	CTRI/2024/03/064435
Sponsor	The Leprosy Mission Trust India
Funder	Indian Council of Medical Research

Submission date: 27/06/2024
Registration date: 08/07/2024
Last edited: 19/08/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
This clinical trial focuses on evaluating the effectiveness and safety of a new treatment for leprosy. Leprosy is a chronic infectious disease caused by the bacterium Mycobacterium leprae. The study aims to determine if the new treatment can reduce the bacterial load, achieve a complete clinical cure, and improve pathological (disease) markers in patients with leprosy.

Who can participate?
Patients aged 15-60 years with multibacillary leprosy who have not received treatment

What does the study involve?
Participants will receive the new treatment and undergo various assessments, including tests measuring bacterial load, clinical examinations to assess lesion regression and overall improvement, and tests to evaluate changes in the Bacillary Index (BI). These assessments will occur at the start of the study and after 3 months, 6 months, and 1 year.

What are the possible benefits and risks of participating?
Benefits:
1. Participants may experience improvement in their leprosy symptoms.
2. Contribution to scientific knowledge that may help future patients with leprosy.
Risks:
1. Possible side effects of the treatment, ranging from mild to severe.
2. Regular follow-up visits and tests may be time-consuming.

Where is the study run from?
The Leprosy Mission Trust India

When is the study starting and how long is it expected to run for?
March 2023 to July 2025

Who is funding the study?
Indian Council of Medical Research

Who is the main contact?
Dr Joydeepa Darlong, joydeepa.darlong@leprosymission.in

Contact information

Dr Joydeepa Darlong
Principal investigator

16, Pandit Pant Marg
CNI Bhavan
New Delhi
110001
India

ORCID ID	0000-0002-3242-8875
Phone	+91 (0)9434885198
Email	joydeepa.darlong@leprosymission.in

Dr Itu Singh
Scientific

Stanley Browne Laboratory
TLM Community Hospital Shahdara
Delhi
110093
India

ORCID ID	0000-0003-0596-8566
Phone	+91 (0)9717730549
Email	itu.singh@leprosymission.in

Dr Reeta Devi
Public

TLM Community Hospital Shahdara
Nand Nagari
Delhi
110093
India

ORCID ID	0000-0002-4107-4271
Phone	+91 (0)6006203600
Email	reeta.devi@leprosymission.in

Dr Samrun Nessa
Public

TLM Community Hospital Shahdara
Delhi
110093
India

Phone	+91 (0)9110322091
Email	samrun.nessa@leprosymission.in

Dr Neeta Maximus
Public

TLM Hospital Barabanki
Barabanki
225001
India

Phone	+91 (0)9936566849
Email	neeta.maximus@leprosymission.in

Dr Vandana Elkana
Public

TLM Chandkhuri
Bilaspur
495222
India

Phone	+91 (0)9981774449
Email	vandana.elkana@leprosymission.in

Dr Utpal Sengupta
Scientific

Stanley Browne Laboratory
TLM Community Hospital Shahdara
Delhi
110093
India

ORCID ID	0000-0002-1177-1076
Phone	+91 (0)9212761651
Email	utpal.sengupta@leprosymission.in

Mr Karthikeyan Govindasamy
Scientific

16, Pandit Pant Marg
CNI bhavan
New Delhi
100001
India

ORCID ID	0000-0001-5500-1308
Phone	+91 (0)9935284315
Email	karthikeyan.g@leprosymission.in

Dr Anamika Haldar
Scientific

The Leprosy Mission Home and Hospital
Purulia, West Bengal
723101
India

Phone	+91 (0)8271855993
Email	anamika.haldar@leprosymission.in

Dr Ann Miriam Jose
Scientific

Molecular Biology Lab
Schieffelin Institute of Health – Research & Leprosy Centre (SIH-R & LC)
Vellore
632106
India

Email	annmjose97@gmail.com

Study information

Primary study design	Interventional
Study design	Open-label randomized clinical control trial
Secondary study design	Randomised controlled trial
Participant information sheet	45703_PIS.pdf
Scientific title	A comparative multicentric non-inferiority clinical trial of WHO multibacillary multidrug therapy with a new monthly chemotherapy regimen containing rifampicin, moxifloxacin and clarithromycin on multibacillary patients from India
Study acronym	RMC
Study objectives	Monthly rifampicin, moxifloxacin and clarithromycin (RMC) are as efficacious and safe as WHO multibacillary multidrug therapy (MBMDT) in patients affected by multibacillary leprosy.
Ethics approval(s)	Approved 20/11/2023, TLMTI ethics Committee (16, Pandit Pant Marg, CNI Bhawan, New Delhi, 110001, India; +91 (0)9811912926; monicathomaschandy@gmail.com), ref: TLMTI/EC/C- 68
Health condition(s) or problem(s) studied	Leprosy
Intervention	It is an open-label randomized clinical control non-inferiority trial where in the intervention group a monthly supervised regimen of rifampicin, moxifloxacin and clarithromycin will be administered in doses of 600 mg, 400 mg, and 1000 mg respectively once a month and the control arm would be given routine WHO MB MDT (rifampicin 600 mg, clofazimine 300 mg once monthly and clofazimine 50 and dapsone 100 mg daily). 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 centers in opaque envelopes. After consent is approved, the envelope will be opened, and the patient will be put on the 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. Slit skin smears of all the study subjects will be collected at baseline, 6 and 12 months and transported in RNA later to the SBL. Real-time PCR will be done to quantitate copy numbers of the genes encoding 16S rRNA, hsp18 and exsA 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 methods at the time of RFT in Schieffelin Institute of Health – Research and Leprosy Centre Karigiri (SIHR&LC), Vellore.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Rifampicin, moxifloxacin, clarithromycin, clofazimine, dapsone
Primary outcome measure(s)	1. Molecular: 1.1. Reduction of copy numbers by molecular viability assay (MVA) measured using quantitative PCR (qPCR) at baseline, 1, 3, 6 and 12 months 1.2. Complete killing of M. leprae assessed using mouse foot pad (MFP) assay at release from treatment (RFT) (12 months) 2. Clinical: 2.1. Complete clinical cure, defined as full regression of the lesions, assessed through clinical examination at baseline, 6 months, and 1 year 2.2. Clinical improvement of the lesions measured by a clinical criterion (e.g., lesion size reduction) at baseline, 6 months, and 1 year 3. Pathological: 3.1. Bacillary Index (BI) improvement measured using skin smears and histopathological examination at baseline, 3 months, 6 months, and 1 year
Key secondary outcome measure(s)	1. Immunological outcomes: 1.1. Neuritis measured through patient self-reporting of pain during interviews and nerve function tests (e.g., sensory and motor function tests) every month during the treatment period and thereafter 6 monthly for 1 year 1.2. Type I reaction assessed through clinical examination and patient reporting with type 1 reaction from the development of the reaction to its subsidence 1.3. Type II reaction assessed through clinical examination and patient reporting with type 2 reaction from the development of the reaction to its subsidence 2. Safety outcomes: 2.1. Severe side effects, defined as side effects that force the patient to stop treatment, monitored and recorded throughout the treatment period (baseline to 1 year) 2.2. Mild to moderate side effects monitored and recorded throughout the treatment period (baseline to 1 year) 3. Qualitative outcomes: 3.1. Impact of leprosy treatment on life assessed using patient interviews and quality of life questionnaires at 1 year 3.2. Perspective towards leprosy treatment assessed using patient interviews and attitude questionnaires at 1 year
Completion date	14/07/2025

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	15 Years
Upper age limit	70 Years
Sex	All
Target sample size at registration	280
Key inclusion criteria	1. Age 15 years and above 2. 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 the Ridley and Jopling classification system 3. Never treated before for leprosy
Key exclusion criteria	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 of giving informed consent due to mental impairment 4. Immunocompromised patients diagnosed with HIV/AIDS and tuberculosis
Date of first enrolment	02/07/2024
Date of final enrolment	31/01/2025

Locations

Countries of recruitment

India

Study participating centres

The Leprosy Mission Home and Hospital

Belguma
Puruliya
723101
India

The Leprosy Mission Hospital

Leprosy Clinic
Barabanki
225001
India

The Leprosy Mission Hospital

Chandkhuri
Chandkhuri
495222
India

TLM Community Hospital

Nandnagari
Delhi
110093
India

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data-sharing plans for the current study are unknown and will be made available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Other files	Standard operating procedure documents		12/08/2024	No	No
Other files		25/08/2023	19/08/2024	No	No
Participant information sheet			01/07/2024	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Additional files

45703_PIS.pdf: Participant information sheet
ISRCTN70846313 SOP documents.zip: Standard operating procedure documents
ISRCTN70846313_Indian Council of Medical Research_Investigator-Initiated Research Proposal_25Aug2023.pdf: Other files

Editorial Notes

19/08/2024: An Indian Council of Medical Research Investigator-Initiated Research Proposal document was uploaded as an additional file.
12/08/2024: A zipped folder of standard operating procedure documents was uploaded as an additional file.
01/07/2024: Study's existence confirmed by the Indian Council of Medical Research.