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CTRI Number  CTRI/2012/06/002716 [Registered on: 06/06/2012] Trial Registered Prospectively
Last Modified On: 03/02/2015
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Study of effectiveness of Stavudine 20mg taken two times daily in patients suffering from HIV-1 infection 
Scientific Title of Study   A Randomised, Double-Blind, Multi-Centre, Parallel-Group Phase 3b Study to Demonstrate Non-inferiority of Stavudine (20 mg Twice Daily)Compared With Tenofovir Disoproxil Fumarate (300 mg Once Daily) When Administered in Combination With Lamivudine and Efavirenz in Antiretroviral-Naive Patients Infected With HIV-1. 
Trial Acronym   
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
WRHI 001 (Version 2 dated 25 Oct 2012)  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Nagalingeswaran Kumarasamy 
Designation  Principal Investigator 
Affiliation  YR Gaitonde Medical Educational & Research Foundation 
Address  YR Gaitonde Medical Educational & Research Foundation, Voluntary Health Services, Rajiv Gandhi Salai, Taramani, Chennai, India.

Chennai
TAMIL NADU
600113
India 
Phone  919381006962  
Fax    
Email  kumarasamy@yrgcare.org  
 
Details of Contact Person
Scientific Query

Modification(s)  
Name  Arun Sundriyal 
Designation  Associate Director, Clinical Management 
Affiliation  PPD Pharmaceutical Development India Pvt. Ltd. 
Address  PPD Pharmaceutical Development India Pvt Ltd., Vatika City Point, 11th floor Sector 25, Mehrauli Gurgaon Road,India

Gurgaon
HARYANA
122002
India 
Phone  91244739903  
Fax  911244739999  
Email  Arun.Sundriyal@ppdi.com  
 
Details of Contact Person
Public Query

Modification(s)  
Name  Arun Sundriyal 
Designation  Associate Director - Clinical Management 
Affiliation  PPD Pharmaceutical Development India Pvt Ltd.  
Address  PPD Pharmaceutical Development India Pvt Ltd., Vatika City Point, 11th floor Sector 25, Mehrauli Gurgaon Road,India

Gurgaon
HARYANA
122002
India 
Phone  911244739903  
Fax  911244739999  
Email  Arun.Sundriyal@ppdi.com  
 
Source of Monetary or Material Support  
Wits Reproductive Health and HIV Institute (WRHI), University of the Witwatersrand, Hillbrow Health Precinct, Hugh Solomon Building, Corner Esselen Street, and Klein Street Hillbrow, 2001, South Africa 
 
Primary Sponsor  
Name  Wits Reproductive Health and HIV Institute WRHI 
Address  University of the Witwatersrand, Hillbrow Health Precinct, Hugh Solomon Building, Corner Esselen Street, and Klein Street Hillbrow, 2001, South Africa 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
PPD Pharmaceutical Development India Pvt Ltd  01-Dynasty B-Wing(Kanakia Spaces) Andheri-Kurla Road, Andheri East, Mumbai, MAHARASHTRA 400059, India  
 
Countries of Recruitment     India
South Africa
Uganda  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Nagalingeswaran Kumarasamy  YR Gaitonde Medical Educational & Research Foundation  I Floor Room # 3 Clinical Trials Unit, YRGCARE Medical Centre VHS Chennai CRS, Voluntary Health Services, Rajiv Gandhi Salai, Taramani, Chennai – 600 113, India.
Chennai
TAMIL NADU 
919381006962

kumarasamy@yrgcare.org 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
YRGCARE Institutional Review Board, Chennai (PI - Dr Nagalingeswaran Kumarasamy)  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Antiretroviral-Naive Patients Infected With HIV-1,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Stavudine (d4T) 20-mg capsules, Twice daily [BID])   Stavudine (d4T) 20-mg Oral capsules, Twice daily [BID]) A 96-week treatment 
Comparator Agent  Tenofovir (TDF) 300 mg Capsules, Once daily [QD]  Tenofovir (TDF) 300 mg Oral Capsules, Once daily [QD], A 96-week treatment 
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1. Patient is male or female aged more than or equal to 18 years (upper limit of less than 65 years in India)

2. Patient has a documented laboratory diagnosis of infection with HIV-1 (positive enzyme-linked
immunosorbent assay HIV-1 antibody test) at screening or from previous records

3. Patient has a life expectancy of more than or equal to 2 years in the opinion of the investigator

4. Patient has a plasma HIV-1 RNA level more than 1000 copies/mL

5. Patient has a plasma CD4 count less than 350 cells/mm3 using standard flow cytometry within 60 days of baseline

6. Patient has the following clinical chemistry and haematological laboratory results at screening:
• Serum creatinine less than or equal 1.5 mg/dL (133 micromol/L) and a calculated creatinine clearance level more than or equal 60 mL/min according to the Cockcroft-Gault formula
• Serum alanine aminotransferase less than 5 × upper limit of normal (ULN)
• Serum aspartate aminotransferase less than 5 × ULN
• Serum lipase less than or equal 1.5 × ULN
Total bilirubin less than or equal 1.5 mg/dL (25 micromol/L) unless felt by clinician to be due to Gilbert syndrome
• Haemoglobin more than or equal 7.0 g/dL
• Absolute neutrophil count more than or equal 500/mm3
• Platelet count more than or equal 50 000/mm3

7. Female patients of childbearing potential, including those who are less than 2 years post-menopausal, must agree to, and comply with using a highly effective method of birth control (eg, barrier contraceptives
[condom or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables,
combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices, or sexual abstinence) while participating in this study. In addition, all women of childbearing potential must agree to continue to use birth control throughout the study until last study visit.
Women Not of Childbearing Potential - Women who are postmenopausal or permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy). Women of Childbearing Potential (WOCBP) - Any female who has experienced menarche and does not meet the criteria for "Women Not of Childbearing Potential".

8. Patient has the ability to comprehend the full nature and purpose of the study, in the opinion of the investigator, including possible risks and side effects, to cooperate with the investigator, to understand verbal and written instructions, and to comply with the requirements of the entire study

9. Patient is informed of the full nature and purpose of the study, including possible risks and side effects, given ample time and opportunity to read and understand this information, and sign and date the written informed consent before inclusion in the study
 
 
ExclusionCriteria 
Details  Patients meeting any of the following criteria will be excluded from the study:

1. Patients who have previously received treatment with any form of ART, including
preventing mother-to-child transmission regimens

2. Patients who are taking and can not discontinue the following prohibited concomitant
medications at least 1 week prior to the baseline visit and for the duration of the study
period:
Patients who are clinically unstable, in the investigator’s opinion, should be stabilized prior to inclusion into this study and their baseline concomitant medications should be stable for at least 1 month (30 days) prior to enrolment. In addition, investigators should not anticipate changing dose levels or medications for the duration of the study. Patients who, in the investigator’s opinion, require HIV-related prophylaxis (such as cotrimoxazole) and/or other HIV-related treatments (e.g. treatment for oral thrush, tuberculosis, etc) and who, in the investigator’s opinion are clinically stable may have such treatment initiated or discontinued during the screening period. The 30-day waiting period will not apply to the latter.
3. Patients who have a current history of drug or alcohol abuse that, in the opinion of the
investigator, may be an impediment to patient adherence to the protocol

4. Patients who have a medical history or evidence of gastrointestinal malabsorption
syndrome, chronic nausea, or vomiting which may prevent patients from receiving oral
medication

5. Patients who have participated in a study with an investigational drug within 60 days of
screening or who are currently receiving treatment with any other investigational drug or
device

6. Patients who are hepatitis B surface antigen positive

7. Patients with symptomatic peripheral neuropathies

8. Female patients who are currently pregnant or breastfeeding

9. Female patients desiring pregnancy during the next 2 years

10. Patients who have a strong likelihood of relocating far enough to make access to the
study site difficult 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded 
Primary Outcome  
Outcome  TimePoints 
The primary efficacy endpoint will be the proportion of patients with undetectable plasma HIV-1 RNA levels (less than 50 copies/mL) at Week 48. Patients who do not have a HIV-1 RNA sample taken at Week 48 will be considered as not having achieved undetectable plasma HIV-1 RNA levels (less than 50 copies/mL) at Week 48.
 
Week 48.
 
 
Secondary Outcome  
Outcome  TimePoints 
Proportion of patients with plasma HIV-1 RNA levels less than 200 copies/mL at Week 96   Week 96 
Time to virologic failure (defined as confirmed HIV-1 RNA levels greater than or equal 1000 copies/mL at Week 12-24 or greater than or equal 200 copies/mL at or after Week 24)  Week 12 - 24 
Proportion of patients in each regimen with undetectable plasma HIV-1 RNA levels (less than 50 copies/mL) at Weeks 48 and 96  Weeks 48 and 96 
Change from baseline in plasma HIV-1 RNA levels by visit.  By visit. 
Change from baseline in plasma CD4 levels by visit  By visit 
 
Target Sample Size   Total Sample Size="1068"
Sample Size from India="356" 
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 3 
Date of First Enrollment (India)
Modification(s)  
25/09/2012 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  30/07/2012 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NA 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary  

This study aims to demonstrate the non-inferiority of a lower dose of d4T compared to TDF over 2 years of therapy, in terms of virological efficacy and early toxicity.


 
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