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CTRI Number  CTRI/2017/12/010951 [Registered on: 21/12/2017] Trial Registered Prospectively
Last Modified On: 25/03/2022
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   Clinical trial comparing High dose rifampicin and Conventional dose of rifampicin in drug sensitive pulmonary tuberculosis patients 
Scientific Title of Study   Phase IIb open label, parallel, randomized controlled clinical trial to evaluate the safety, tolerability, pharmacokinetics and anti-bacterial activity of High dose rifampicin versus Conventional dose of Rifampicin along with standard anti-tubercular therapy (ATT) in drug sensitive adult patients of pulmonary tuberculosis 
Trial Acronym  HICON -R 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Bhavani P K  
Designation  Scientist D 
Affiliation  National Institute for research in Tuberculosis 
Address  National Institute for Research in Tuberculosis No 1 Mayor Sathyamoorthy Road Chetpet Chennai
No 1 Mayor Sathyamoorthy Road Chetpet Chennai
Chennai
TAMIL NADU
600031
India 
Phone  9962934169  
Fax  914428362525  
Email  bhavani.pk@nirt.res.in  
 
Details of Contact Person
Scientific Query  
Name  Dr Bhavani P K  
Designation  Scientist D 
Affiliation  National Institute for research in Tuberculosis 
Address  National Institute for Research in Tuberculosis No 1 Mayor Sathyamoorthy Road Chetpet Chennai
No 1 Mayor Sathyamoorthy Road Chetpet Chennai
Chennai
TAMIL NADU
600031
India 
Phone  9962934169  
Fax  914428362525  
Email  bhavani.pk@nirt.res.in  
 
Details of Contact Person
Public Query  
Name  Dr Bhavani P K  
Designation  Scientist D 
Affiliation  National Institute for research in Tuberculosis 
Address  National Institute for Research in Tuberculosis No 1 Mayor Sathyamoorthy Road Chetpet Chennai
No 1 Mayor Sathyamoorthy Road Chetpet Chennai
Chennai
TAMIL NADU
600031
India 
Phone  9962934169  
Fax  914428362525  
Email  bhavani.pk@nirt.res.in  
 
Source of Monetary or Material Support  
Indian Council of Medical Research(ICMR) - India TB Research Consortium (ITRC) V. Ramalingaswami Bhawan P.O. Box No. 4911 Ansari Nagar New Delhi - 110029 India 
 
Primary Sponsor  
Name  India TB Research Consortium 
Address  Indian Council of Medical Research V. Ramalingaswami Bhawan P.O. Box No. 4911. Ansari Nagar New Delhi - 110029.  
Type of Sponsor  Research institution 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 4  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Surya Kanth  King Georges Medical University  Department of Thoracic Medicine Shah Mina Road, Chowk, Lucknow, Uttar Pradesh 226003
Lucknow
UTTAR PRADESH 		 522-2257450

skantpulmed@gmail.com 
Dr Bhavani P K  National Institute for Research in Tuberculosis  Department of Clinical Research No 1 Mayor Sathyamoorthy Road Chetpet, Chennai - 600 031
Chennai
TAMIL NADU 		 044-28369500
044-28362525
bhavani.pk@nirt.res.in 
Dr Jitendra Kumar Saini  National Institute of TB and Respiratory Diseases  Department of Thoracic Medicine Sri Aurobindo Marg, Near Qutub Minar, Mehrauli, New Delhi, Delhi 110030
New Delhi
DELHI 		 26517826
26517834
jk.saini@nitrd.nic.in 
Dr Ashutosh Nath Aggarwal  Post Graduate Institute of Medical Education and Research  Department of Thoracic Medicine PGIMER,Sector-12 Chandigarh - 160 012, India
Chandigarh
CHANDIGARH 		 172-2747585
172-2744401
Aggarwal.ashutosh@outlook.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 5  
Name of Committee  Approval Status 
Institutional Ethics committe King George Medical University Lucknow  Approved 
Institutional Ethics Committee Bhagwan Mahavir Medical Research Centre   Approved 
Institutional Ethics committee National Institute for Thoracic and Respiratory Diseases, New Delhi  Approved 
Institutional Ethics committee PGI Chandigarh  Approved 
NIRT Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  Adult Sputum smear positive Pulmonary TB patients, (1) ICD-10 Condition: A150||Tuberculosis of lung,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Rifampicin 10 mg /kg body OD for 2 months  Control regimen : Rifampicin (10mg/kg/day), Isoniazid, Pyrazinamide and Ethambutol daily for 2 months followed by Rifampicin (10mg/kg/day), Isoniazid and Ethambutol daily for 4 months (2R(10)HZE / 4R(10)HE).  
Intervention  Rifampicin 25 mg/kg body weight OD for 2 months,Rifampicin 35 mg/kg body weight OD for 2 months  (1) High dose Rifampicin (25mg/kg/day), Isoniazid, Pyrazinamide and Ethambutol, daily for 2 months in intensive phase. This will be followed by conventional dose Rifampicin (10mg/kg/day), Isoniazid and Ethambutol daily for 4 months (2 R(25)HZE/ 4 R(10) HE) (2) High dose Rifampicin (35mg/kg/day), Isoniazid, Pyrazinamide and Ethambutol, daily for 2 months in intensive phase. This will be followed by conventional dose of Rifampicin (10 mg/kg/day), Isoniazid and Ethambutol daily for 4 months (2 R (35) HZE/ 4 R(10) HE) 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  60.00 Year(s)
Gender  Both 
Details  Residing in or around the study sites
No prior history of ATT (or < 15 days of ATT)
At least 2 sputum smears should be positive for TB bacilli
At least 1 sputum should be RMP /INH sensitive by GeneXpert /LPA
Express willingness to attend the treatment centre for supervised treatment
Express willingness to give written informed consent
 
 
ExclusionCriteria 
Details  Body weight < 30 kgs or > 65 kgs
Hepatic or renal disease
history of liver disease,
current ALT > 2.5 times ULN
total bilirubin >1.2 times ULN
Serum Creatinine >1.2 mg/dL
Blood Urea >43 mg/dL
Haemoglobin <7.0 g/dL or platelet count <150,000/mm3, or WBC <4500 cells/μL
Psychiatric illness
History of seizure or loss of consciousness
Seriously ill (Karnofsky scale <50)
Sero-positive for HIV virus antibodies
Serology positive for HBS Ag or Hepatitis C virus antibody
Pregnancy or lactation
Diabetics on Insulin
 
 
Method of Generating Random Sequence   Permuted block randomization, variable 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
The proportion of participants with treatment emergent adverse events with high dose RMP, 25 or 35 mg/kg/daily, (intervention arm) versus the standard 10 mg/kg dose of rifampicin (control arm) when given daily along with other first-line anti-TB drugs during the 8 -weeks anti-TB treatment of new sputum smear and culture positive PTB
 		 2 months (8weeks) 
 
Secondary Outcome  
Outcome  TimePoints 
Drug concentrations and PK parameters of RMP between trial regimens
Proportion of patients with negative sputum cultures every week till 2nd month and at 3rd ,4th month and at end of treatment
Time to sputum culture conversion
To evaluate rate of change in time to sputum culture positivity across the treatment arms over 8 and 16 weeks of treatment period
Identification of predictive biomarkers of drug induced liver injury


 		 2 months and at 18 months 
 
Target Sample Size   Total Sample Size="327"
Sample Size from India="327" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   22/01/2018 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details
Modification(s)  		 Submitted to Lancet Infectious Diseases Journal 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary   Despite wide implementation of highly efficacious regimen TB still remains a global health emergency as current 6 month period of treatment poses formidable challenges to the programme. Rifampicin is a unique drug explored widely for shortening TB treatment and it also cheaper and is being manufactured by generic companies. Using High dose Rifampicin is one such approach.Additionally there is in-vitro, animal and human evidence from different ethnic populations that higher than standard dose of Rifampicin can be safely and successfully used to shorten he treatment duration and reduces relapses and causes early culture conversion.Also pharmacokinetic studies from our institute have shown that current dosages are sub therapeutic and imapacts the treatment outcomes. But there is sparse data on safety and pharmacokinetics from Indian population so we propose to undertake this trial to investigate the effect of high dose Rifampicin on the safety tolerability and PK comparing with the conventional dose of Rifampicin in treating pulmonary TB patients
 
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