| CTRI Number |
CTRI/2012/06/002716 [Registered on: 06/06/2012] Trial Registered Prospectively |
| Last Modified On: |
10/09/2023 |
| 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
|
|
|
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)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
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.
|