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Trial to Assess the Impact of PrEP to Tenofovir Gel on the Efficacy of Tenofovir-containing ART on Viral Suppression (TOAST)

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ClinicalTrials.gov Identifier: NCT01387022
Recruitment Status : Completed
First Posted : July 1, 2011
Results First Posted : March 20, 2017
Last Update Posted : April 20, 2017
Sponsor:
Information provided by (Responsible Party):
Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Antiretroviral Treatment Outcomes
Intervention Drug: Tenofovir, lamivudine and efavirenz
Enrollment 59
Recruitment Details Two arm, open-label, randomised controlled trial
Pre-assignment Details A total of 214 participants were assessed for eligibility: 60 were excluded due to high CD4+ count, 30 were already on ART, 8 were loss to follow-up and 43 refused participation. Of the 73 that were screened, 8 were screen failures due to high CD4+ count, 4 refused participation, 1 was very ill with TB and 1 could not be contacted.
Arm/Group Title Tenofovir-containing Regimen Tenofovir-sparing Regimen
Hide Arm/Group Description Patients were initiated on EFV, FTC/3TC,TDF Patients were initiated on EFV,FTC/3TC,ZDV
Period Title: Overall Study
Started 29 30
Completed 28 26
Not Completed 1 4
Reason Not Completed
Death             1             1
Lost to Follow-up             0             3
Arm/Group Title Tenofovir-containing Regimen Tenofovir-sparing Regimen Total
Hide Arm/Group Description Patients were initiated on EFV, FTC/3TC,TDF Patients were initiated on EFV,FTC/3TC,ZDV Total of all reporting groups
Overall Number of Baseline Participants 29 30 59
Hide Baseline Analysis Population Description
All participants who were randomised and initiated on ART
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 29 participants 30 participants 59 participants
28
(25 to 33)
28
(26 to 30)
28
(25 to 32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 30 participants 59 participants
Female
29
 100.0%
30
 100.0%
59
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 30 participants 59 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
29
 100.0%
30
 100.0%
59
 100.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
South Africa Number Analyzed 29 participants 30 participants 59 participants
29 30 59
CD4+ T cell count  
Median (Inter-Quartile Range)
Unit of measure:  cells/uL
Number Analyzed 29 participants 30 participants 59 participants
345
(289 to 431)
335
(280 to 411)
345
(280 to 423)
Viral load  
Mean (Standard Deviation)
Unit of measure:  Log10 copies/ml
Number Analyzed 29 participants 30 participants 59 participants
4.4  (0.79) 4.6  (0.80) 4.5  (0.79)
1.Primary Outcome
Title The Antiretroviral Treatment Failure Rate at 12 Months.
Hide Description Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death
Time Frame 12 months post ART intiation or until time of death
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who randomised and initiated on ART
Arm/Group Title Tenofovir-containing Regimen Tenofovir-sparing Regimen
Hide Arm/Group Description:
Patients were initiated on EFV, FTC/3TC,TDF
Patients were initiated on EFV,FTC/3TC,ZDV
Overall Number of Participants Analyzed 29 30
Measure Type: Number
Unit of Measure: participants
4 5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tenofovir-containing Regimen, Tenofovir-sparing Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title Change in CD4+ Cell Count From Randomisation to 12 Months Post-randomisation
Hide Description Difference between 12 months and randomisation CD4+ count was calculated and then summarised
Time Frame Measured at 12 months post ART initiation
Hide Outcome Measure Data
Hide Analysis Population Description
All participants for whom CD4+ count measurements were recorded at randomisation and at 12 months
Arm/Group Title Tenofovir-containing Regimen Tenofovir-sparing Regimen
Hide Arm/Group Description:
Patients were initiated on EFV, FTC/3TC,TDF
Patients were initiated on EFV,FTC/3TC,ZDV
Overall Number of Participants Analyzed 21 19
Median (Inter-Quartile Range)
Unit of Measure: cells/uL
217
(52 to 272)
174
(70 to 404)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tenofovir-containing Regimen, Tenofovir-sparing Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.481
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Secondary Outcome
Title Tenofovir Resistance, Defined as Presence of K65R, K70E or Any of the TAMS Mutations
Hide Description [Not Specified]
Time Frame From randomisation until either time of termination or time of death
Hide Outcome Measure Data
Hide Analysis Population Description
Resistance testing was only done on participants who were failing first line antiretroviral therapy.
Arm/Group Title Tenofovir-containing Regimen Tenofovir-sparing Regimen
Hide Arm/Group Description:
Patients were initiated on EFV, FTC/3TC,TDF
Patients were initiated on EFV,FTC/3TC,ZDV
Overall Number of Participants Analyzed 1 1
Measure Type: Count of Participants
Unit of Measure: Participants
1
 100.0%
1
 100.0%
4.Secondary Outcome
Title Reported Adverse Events With Severity Grades 3 and 4 Based on the DAIDS Toxicity Grading Tables
Hide Description [Not Specified]
Time Frame From randomisation until either time of termination or time of death
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who randomised and initiated on ART
Arm/Group Title Tenofovir-containing Regimen Tenofovir-sparing Regimen
Hide Arm/Group Description:
Patients were initiated on EFV, FTC/3TC,TDF
Patients were initiated on EFV,FTC/3TC,ZDV
Overall Number of Participants Analyzed 29 30
Measure Type: Count of Participants
Unit of Measure: Participants
7
  24.1%
12
  40.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tenofovir-containing Regimen, Tenofovir-sparing Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.267
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Cellular and Humoral Immune Responses
Hide Description We will assess whether exposure to tenofovir gel at the time of HIV acquisition alters the subsequent humoral and cellular immune responses following antiretroviral treatment initiation
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for this Outcome Measure
Arm/Group Title Tenofovir-containing Regimen Tenofovir-sparing Regimen
Hide Arm/Group Description:
Patients were initiated on EFV, FTC/3TC,TDF
Patients were initiated on EFV,FTC/3TC,ZDV
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Genital Viral Shedding (Viral Load on Tear Flow)
Hide Description [Not Specified]
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for this Outcome Measure
Arm/Group Title Tenofovir-containing Regimen Tenofovir-sparing Regimen
Hide Arm/Group Description:
Patients were initiated on EFV, FTC/3TC,TDF
Patients were initiated on EFV,FTC/3TC,ZDV
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 19 July 2011 to 30 September 2014
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tenofovir-containing Regimen Tenofovir-sparing Regimen
Hide Arm/Group Description Patients were initiated on EFV, FTC/3TC,TDF Patients were initiated on EFV,FTC/3TC,ZDV
All-Cause Mortality
Tenofovir-containing Regimen Tenofovir-sparing Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Tenofovir-containing Regimen Tenofovir-sparing Regimen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/29 (34.48%)      11/30 (36.67%)    
Blood and lymphatic system disorders     
Anaemia * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Neutropenia * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Pancytopenia * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Cardiac disorders     
Cardiac arrest * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
General disorders     
Malaise * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Infections and infestations     
Appendicitis perforated * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Pelvic inflammatory disease * 1  1/29 (3.45%)  1 0/30 (0.00%)  0
Metabolism and nutrition disorders     
Hyperlactacidaemia * 1  0/29 (0.00%)  0 1/30 (3.33%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign hydatidiform mole * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Nervous system disorders     
Headache * 1  1/29 (3.45%)  1 0/30 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Delivery * 1  5/29 (17.24%)  5 1/30 (3.33%)  1
Premature labour * 1  1/29 (3.45%)  1 0/30 (0.00%)  0
Psychiatric disorders     
Completed suicide * 1  1/29 (3.45%)  1 0/30 (0.00%)  0
Surgical and medical procedures     
Abscess drainage * 1  1/29 (3.45%)  1 0/30 (0.00%)  0
Caesarean section * 1  2/29 (6.90%)  2 3/30 (10.00%)  3
Female sterilisation * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tenofovir-containing Regimen Tenofovir-sparing Regimen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/29 (3.45%)      5/30 (16.67%)    
Gastrointestinal disorders     
Abdominal pain * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Infections and infestations     
Bartholin's abscess * 1  1/29 (3.45%)  1 0/30 (0.00%)  0
Metabolism and nutrition disorders     
Abnormal loss of weight * 1  0/29 (0.00%)  0 2/30 (6.67%)  2
Hypophosphataemia * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Musculoskeletal and connective tissue disorders     
Muscle spasms * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Myalgia * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Nervous system disorders     
Dizziness * 1  0/29 (0.00%)  0 1/30 (3.33%)  1
Psychiatric disorders     
Depression * 1  0/29 (0.00%)  0 2/30 (6.67%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
The main limitation of the study was the small sample size. The eligible pool of participants was dependent on two other tenofovir gel trials, one of which experienced long delay in starting.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Head of Statistics and Data Management
Organization: CAPRISA
Phone: +27 31 260 4392
EMail: nonhlanhla.yende@caprisa.org
Publications:
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. December 1, 2009. Available from: www.aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf. Accessed 9 November 2010.
Layout table for additonal information
Responsible Party: Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa
ClinicalTrials.gov Identifier: NCT01387022     History of Changes
Other Study ID Numbers: CAPRISA 009
First Submitted: June 21, 2011
First Posted: July 1, 2011
Results First Submitted: January 30, 2017
Results First Posted: March 20, 2017
Last Update Posted: April 20, 2017