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Trial registered on ANZCTR


Registration number
ACTRN12613000834752
Ethics application status
Approved
Date submitted
12/07/2013
Date registered
30/07/2013
Date last updated
30/07/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of complementary effect of traditional medicine formulation to Category II regime in Tuberculosis (TB) treatment
Scientific title
Randomized controlled trial of traditional medicine as complementary to Category II regime on treatment of tuberculosis
Secondary ID [1] 282813 0
World Health Organization( Myanmar)
SEMMR 1207369 (WHO/APW)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tuberculosis
289588 0
Condition category
Condition code
Alternative and Complementary Medicine 289925 289925 0 0
Herbal remedies
Infection 289989 289989 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Traditional medicine (four plant extracts prepared in two capsules) plus standard category II regime (4 FDC - Rifampicin plus Isoniazid plus Pyrazinamide, Ethambutol plus Injection Streptomycin) for 150 category II pulmonary TB patients.
The trial drugs contain alkaloids, flavonoids and tannins. One dose contains plant 1 extract 233 mg, plant 2 extract 96 mg, plant 3 extract 34 mg and plant 4 extract 10.4 mg.plant 1 is Azardichata indica , plant 2 is Desmodium triquetrium plant 3 is Alpinia galaca, and plant 4 is Acorus calamus. All drugs will be given once a day at evening for 8 months duration. The monitoring will be done by counting of capsules returned and family member/voluntary health workers will observe regular taking of trial drugs by subjects.
Intervention code [1] 287497 0
Treatment: Other
Comparator / control treatment
Placebo (three capsules containing starch) plus standard Category II regime for 150 category II pulmonary TB patients
Control group
Placebo

Outcomes
Primary outcome [1] 289982 0
Proportions of patients with sputum smear negativity at three months of intervention
Timepoint [1] 289982 0
at three months of intervention
Secondary outcome [1] 303703 0
– (i) Proportions of patients with improvement in Chest-X-ray
Timepoint [1] 303703 0
at three months of intervention
Secondary outcome [2] 303820 0
Proportions of patients with adverse events such as renal function impairment, liver function impairment and impairment of integumentary system.
Timepoint [2] 303820 0
at three months of intervention
Secondary outcome [3] 303821 0
Proportions of patients with weight gain that will be assessed by using calibrated digital weighing machine in all visits
Timepoint [3] 303821 0
Monthly throughout the 8 intervention period

Eligibility
Key inclusion criteria
- Sputum smear positive patients at the start of Cat II regime at TB centres under National Tuberculosis Control Programme
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Severe liver, kidney and/or bone marrow disorders as diagnosed by medical officer based on biochemical laboratory tests (Blood for complete picture, liver function tests, renal function tests)
b) History of diabetes, hypertension, hepatitis B infection, hepatitis C infection, HIV
c) History of taking steroids or anti-cancer drugs within one month
d) Acute medical or surgical complications which require hospitalization
e) Pregnancy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
- After obtaining informed consent from the eligible Cat II patients, screening form will be used for history taking, physical examination and laboratory investigations for recruitment.
- Eligible patients will then be asked to participate in the lottery system in the block randomization procedure.

Subject will be screened only after explaining the purpose and the schedule of the study and obtaining a written informed consent from him/her.
Baseline demographic, clinical and laboratory investigations will be done at the start of patient recruitment and will be recorded. Subjects will be recruited randomly into two groups. One group will receive 3 capsules of traditional medicine with Cat II regime and another group will be received 3 capsules of placebo with Cat II regime for 8 months.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomization will be used with three trial drug and three placebo in each block.

Preparation will be made to conceal allocation on type of treatment received. The capsules and the bottle containing capsules will be prepared to have the same appearance for treatment group and placebo group. Identification number (id) will be prepared for these bottles by the investigator so that no one except the investigator knows the type of treatment received among patients. Computer generated block randomization method will be used and each block will have an equal number of treatment and placebo

Envelopes will be used to put the pieces of papers. Each envelope will consist of a piece of paper on which the number is indicated to select coded bottle of trial drug or placebo.
Eight envelopes containing eight serial numbers will be packed together so that each packet will consist of eight numbers and there will be 38 packets of envelopes for total 300 patients.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5186 0
Myanmar
State/province [1] 5186 0
Yangon

Funding & Sponsors
Funding source category [1] 287595 0
Other
Name [1] 287595 0
WHO (Technical service agreement)
Address [1] 287595 0
WHO Local representative office of Myanmar, 13th floor, Trader Hotel, Pebadan township, Yangon, Myanmar
Country [1] 287595 0
Myanmar
Primary sponsor type
Other
Name
WHO (Technical service agreement)
Address
WHO Local representative office of Myanmar, 13th floor, Trader Hotel, Pebadan township, Yangon, Myanmar
Country
Myanmar
Secondary sponsor category [1] 286344 0
Government body
Name [1] 286344 0
Department of Medical Research (Lower Myanmar) (DMR-LM), Ministry of Health, Myanmar
Address [1] 286344 0
Department of Medical Research (Lower Myanmar), Ministry of Health, Myanmar
No. 5, Ziwaka Road, Dagon PO-11191, Yangon, Myanmar
Country [1] 286344 0
Myanmar
Other collaborator category [1] 277522 0
Government body
Name [1] 277522 0
National Tuberculosis Control Programme,Department of Health, Ministry of Health, Myanmar
Address [1] 277522 0
Infectious disease control programme, 1000 beded Hospital, Nay Pyi Daw, Ministry of Health, Myanmar
Country [1] 277522 0
Myanmar

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289571 0
Ethical Review Committee on Medical Research involving Human Subjects, Department of Medical Research (Lower Myanmar)
Ethics committee address [1] 289571 0
No.5, Ziwaka Road, Dagon PO, Yangon, Myanmar
Ethics committee country [1] 289571 0
Myanmar
Date submitted for ethics approval [1] 289571 0
Approval date [1] 289571 0
Ethics approval number [1] 289571 0
27 Ethics 2012

Summary
Brief summary
The general objective of the present study is to evaluate the efficacy and safety of four Myanmar medicinal plants on tuberculosis patients, both in terms of therapeutics (sputum conversion and chest X-ray improvement, etc.). A double-blind randomized controlled trial will be carried out on 300 Category II pulmonary tuberculosis patients to deliver standard anti-TB drugs for CAT II therapy plus capsule containing traditional medicine for 150 patients in one group. Another group will receive CAT II therapy with placebo capsule containing 500 mg starch. The capsules of placebo will look similar to the capsule of traditional medicine.

Subjects will be recruited from the Outpatient Departments/National TB Program areas. Baseline demographic characteristics, clinical and laboratory investigations will be done at the start of patient recruitment and will be recorded in all 11 visits (screening visit, day of initiation of the trial, follow-up visits in weeks from initiation of treatment - 1, 4, 8, 12, 16, 20, 24, 28, 32).
They will be instructed to consume 3 capsules once a day (evening). Medication compliance will be documented by pill counting at all visits. Unused medication will be checked and taken back.


Treatment evaluation will be assessed by sputum clearance time, radiographic improvement, weight gain, incidence of adverse events by each visit. The efficacy and safety data will be analysed using ‘Intention to Treat’ analysis. Statistical analysis will be done using Chi-squared test. The level of significance for all analysis will be taken as p<0.05. Interim analysis of recruited patients will be carried out at three monthly intervals. Multivariable logistic regression analysis will be performed. The research findings will provide national TB programme to support treatment of TB by traditional medicine and help in prevention of MDR-TB.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41354 0
Dr Khin Chit
Address 41354 0
Pharmaceutical Toxicology Research Division, Department of Medical Research (Lower Myanmar)
No. 5, Ziwaka Road, Dagon PO 11191, Yangon, Myanmar.
Country 41354 0
Myanmar
Phone 41354 0
95-9-5113451
Fax 41354 0
Email 41354 0
drkhinchit@gmail.com
Contact person for public queries
Name 41355 0
Dr Khin Chit
Address 41355 0
Pharmaceutical Toxicology Research Division, Department of Medical Research (Lower Myanmar)
No. 5, Ziwaka Road, Dagon PO 11191, Yangon, Myanmar.
Country 41355 0
Myanmar
Phone 41355 0
95-9-5113451
Fax 41355 0
Email 41355 0
drkhinchit@gmail.com
Contact person for scientific queries
Name 41356 0
Dr Khin Chit
Address 41356 0
Pharmaceutical Toxicology Research Division, Department of Medical Research (Lower Myanmar)
No. 5, Ziwaka Road, Dagon PO 11191, Yangon, Myanmar.
Country 41356 0
Myanmar
Phone 41356 0
95-9-5113451
Fax 41356 0
Email 41356 0
drkhinchit@gmail.com

No information has been provided regarding IPD availability
Summary results
No Results