Trial Outcomes & Findings for TOTEM: Switch From Other Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to Once Daily Truvada (NCT NCT00323492)
NCT ID: NCT00323492
Last Updated: 2010-01-20
Results Overview
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
92 participants
Primary outcome timeframe
Baseline to Week 12
Results posted on
2010-01-20
Participant Flow
Participant milestones
| Measure |
Truvada
Truvada + nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI).
|
Maintain Baseline Regimen
Maintain baseline regimen.
|
Delayed Truvada
Truvada + NNRTI or PI (participants from the control group who switched NRTIs to Truvada during Study Phase 2).
|
|---|---|---|---|
|
Study Phase 1
STARTED
|
47
|
45
|
0
|
|
Study Phase 1
Intent-to-Treat (ITT) Analysis Set
|
46
|
45
|
0
|
|
Study Phase 1
COMPLETED
|
45
|
45
|
0
|
|
Study Phase 1
NOT COMPLETED
|
2
|
0
|
0
|
|
Study Phase 2
STARTED
|
44
|
18
|
25
|
|
Study Phase 2
COMPLETED
|
40
|
17
|
24
|
|
Study Phase 2
NOT COMPLETED
|
4
|
1
|
1
|
Reasons for withdrawal
| Measure |
Truvada
Truvada + nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI).
|
Maintain Baseline Regimen
Maintain baseline regimen.
|
Delayed Truvada
Truvada + NNRTI or PI (participants from the control group who switched NRTIs to Truvada during Study Phase 2).
|
|---|---|---|---|
|
Study Phase 1
Adverse Event
|
2
|
0
|
0
|
|
Study Phase 2
Adverse Event
|
1
|
0
|
0
|
|
Study Phase 2
Physician Decision
|
1
|
0
|
0
|
|
Study Phase 2
Lost to Follow-up
|
1
|
0
|
0
|
|
Study Phase 2
Withdrawal by Subject
|
0
|
1
|
0
|
|
Study Phase 2
Noncompliance with study schedule
|
0
|
0
|
1
|
|
Study Phase 2
Protocol Violation
|
1
|
0
|
0
|
Baseline Characteristics
TOTEM: Switch From Other Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to Once Daily Truvada
Baseline characteristics by cohort
| Measure |
Truvada
n=47 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=45 Participants
Maintain baseline regimen.
|
Total
n=92 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
49.0 years
INTER_QUARTILE_RANGE 10.7 • n=5 Participants
|
43.0 years
INTER_QUARTILE_RANGE 7.7 • n=7 Participants
|
47.0 years
INTER_QUARTILE_RANGE 9.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
47 participants
n=5 Participants
|
45 participants
n=7 Participants
|
92 participants
n=5 Participants
|
|
Participants with plasma HIV-1 RNA < 400 copies/mL
|
47 participants
n=5 Participants
|
45 participants
n=7 Participants
|
92 participants
n=5 Participants
|
|
Cluster determinant 4 (CD4) cell count
|
467 cells/mm^3
n=5 Participants
|
559 cells/mm^3
n=7 Participants
|
528 cells/mm^3
n=5 Participants
|
|
Low density lipoprotein cholesterol (LDL-CHO)
|
4.0 mmol/L
n=5 Participants
|
4.0 mmol/L
n=7 Participants
|
4.0 mmol/L
n=5 Participants
|
|
Triglycerides
|
2.3 mmol/L
n=5 Participants
|
2.7 mmol/L
n=7 Participants
|
2.4 mmol/L
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: ITT. Last post-baseline observation carried forward (LOCF) method was used for the analysis if the Week 12 value was missing. A missing datum were replaced by the last post-baseline value.
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=44 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=45 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Change From Baseline to Week 12 in Fasting Triglycerides
|
-0.5 mmol/L
Interval -1.2 to 0.0
|
-0.1 mmol/L
Interval -0.8 to 0.3
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: ITT. LOCF method was used for the analysis if the Week 12 value was missing. A missing datum were replaced by the last post-baseline value.
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=44 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=45 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Change From Baseline to Week 12 in Fasting Low-density Lipoprotein Cholesterol (LDL-CHO)
|
-0.4 mmol/L
Interval -1.0 to 0.1
|
-0.1 mmol/L
Interval -0.5 to 0.4
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: ITT. Missing values were excluded.
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=44 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=44 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Change From Baseline to Week 12 in Fasting High-density Lipoprotein Cholesterol (HDL-CHO)
|
-0.1 mmol/L
Interval -0.2 to 0.1
|
0.0 mmol/L
Interval 0.0 to 0.1
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: ITT. Missing values were excluded.
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=44 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=44 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Change From Baseline to Week 12 in Fasting Total Cholesterol (T-CHO)
|
-0.8 mmol/L
Interval -1.3 to -0.1
|
-0.1 mmol/L
Interval -0.7 to 0.5
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: ITT. Missing values were excluded.
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=44 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=44 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Change From Baseline to Week 12 in Fasting T-CHO/HDL-CHO
|
-0.5 Ratio
Interval -0.7 to 0.2
|
-0.1 Ratio
Interval -0.8 to 0.3
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: ITT. Missing values were excluded.
Centralized laboratory assessment. Change = Week 12 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=44 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=44 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Change From Baseline to Week 12 in Fasting HDL-CHO/LDL-CHO
|
0.0 Ratio
Interval 0.0 to 0.0
|
0.0 Ratio
Interval 0.0 to 0.1
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: ITT. Missing values were excluded. Assessment of us-CRP was added to the study schedule via protocol amendment part way through the study. This resulted in small numbers of subjects having data available for this analysis.
Local laboratory assessment. Change = Week 12 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=16 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=7 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Change From Baseline to Week 12 in Fasting Ultra-sensitive C-reactive Protein (Us-CRP)
|
0.4 mg/L
Interval -0.5 to 0.9
|
0.7 mg/L
Interval -3.2 to 2.5
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: ITT. Missing values were excluded.
Centralized laboratory assessment
Outcome measures
| Measure |
Truvada
n=44 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=44 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Percentage of Participants With Fasting Plasma Triglycerides > 10 g/L (> 11.29 mmol/L) at Week 12
|
0 Percentage of participants
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: ITT. Missing values were excluded.
Change = Week 12 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=44 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=44 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Change From Baseline to Week 12 in Cluster Determinant 4 (CD4) Cell Count
|
17.5 cells/mm^3
Interval -36.0 to 63.5
|
16.0 cells/mm^3
Interval -31.0 to 92.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: ITT. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=39 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=16 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Change From Baseline to Week 48 in CD4 Cell Count
|
35.0 cells/mm^3
Interval -37.0 to 116.0
|
40.0 cells/mm^3
Interval -41.5 to 79.5
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: ITT. Missing values were treated as failure.
Outcome measures
| Measure |
Truvada
n=46 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=45 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Percentage of Participants With Virologic Control (Plasma HIV-1 Ribonucleic Acid [RNA] < 400 Copies/mL) at Week 12
|
96 Percentage of participants
|
98 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: ITT. Missing values were excluded. Any subjects with plasma HIV-1 RNA greater than or equal to 400 copies/mL at Week 12 were to have virologic genotyping performed.
Outcome measures
| Measure |
Truvada
n=46 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=45 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to 400 Copies/mL at Week 12
|
0 Percentage of participants
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: ITT. Missing values were treated as failure.
Outcome measures
| Measure |
Truvada
n=46 Participants
Truvada + NNRTI or PI.
|
Maintain Baseline Regimen
n=20 Participants
Maintain baseline regimen.
|
|---|---|---|
|
Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48
|
80 Percentage of participants
|
80 Percentage of participants
|
Adverse Events
Truvada
Serious events: 7 serious events
Other events: 15 other events
Deaths: 0 deaths
Maintain Baseline Regimen
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
All Truvada
Serious events: 7 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Truvada
n=47 participants at risk
Truvada + NNRTI or PI. The number of participants at risk is the number who started the study by switching to Truvada. Participants in this group were to remain on Truvada for 48 weeks (duration of the study). The number at risk was reduced only by study discontinuation (from 47 at baseline to 40 who completed Study Phase 2).
|
Maintain Baseline Regimen
n=45 participants at risk
Maintain baseline regimen. The number of participants at risk is the number who started the study by maintaining their baseline regimen. Per protocol, participants in this group were allowed to switch to Truvada after Week 12 (Delayed TVD group), therefore the number of participants at risk declines over time (from 45 at baseline to 17 who completed Study Phase 2; with most participants switching to Truvada at Week 12).
|
All Truvada
n=72 participants at risk
Truvada + NNRTI or PI (all participants who received Truvada during the study, i.e., participants in the Truvada and Delayed Truvada groups). The number of participants at risk is the number who started the study by switching to Truvada (Truvada group), plus those who started the study by maintaining their baseline regimen but who switched to Truvada during the study (Delayed Truvada group). The number of participants at risk increases over time (from 47 at baseline to 72 when the last switch to Truvada took place; 25 participants switched to Truvada from the "maintain baseline regimen" group in Study Phase 2).
|
|---|---|---|---|
|
Renal and urinary disorders
Nephrolithiasis
|
2.1%
1/47
|
0.00%
0/45
|
1.4%
1/72
|
|
Renal and urinary disorders
Renal failure
|
4.3%
2/47
|
0.00%
0/45
|
2.8%
2/72
|
|
Renal and urinary disorders
Renal impairment
|
2.1%
1/47
|
0.00%
0/45
|
1.4%
1/72
|
|
Renal and urinary disorders
Tubulointerstitial Nephritis
|
2.1%
1/47
|
0.00%
0/45
|
1.4%
1/72
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
2.1%
1/47
|
2.2%
1/45
|
1.4%
1/72
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
2.1%
1/47
|
0.00%
0/45
|
1.4%
1/72
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/47
|
2.2%
1/45
|
0.00%
0/72
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma
|
2.1%
1/47
|
0.00%
0/45
|
1.4%
1/72
|
|
Nervous system disorders
Sciatica
|
0.00%
0/47
|
2.2%
1/45
|
0.00%
0/72
|
Other adverse events
| Measure |
Truvada
n=47 participants at risk
Truvada + NNRTI or PI. The number of participants at risk is the number who started the study by switching to Truvada. Participants in this group were to remain on Truvada for 48 weeks (duration of the study). The number at risk was reduced only by study discontinuation (from 47 at baseline to 40 who completed Study Phase 2).
|
Maintain Baseline Regimen
n=45 participants at risk
Maintain baseline regimen. The number of participants at risk is the number who started the study by maintaining their baseline regimen. Per protocol, participants in this group were allowed to switch to Truvada after Week 12 (Delayed TVD group), therefore the number of participants at risk declines over time (from 45 at baseline to 17 who completed Study Phase 2; with most participants switching to Truvada at Week 12).
|
All Truvada
n=72 participants at risk
Truvada + NNRTI or PI (all participants who received Truvada during the study, i.e., participants in the Truvada and Delayed Truvada groups). The number of participants at risk is the number who started the study by switching to Truvada (Truvada group), plus those who started the study by maintaining their baseline regimen but who switched to Truvada during the study (Delayed Truvada group). The number of participants at risk increases over time (from 47 at baseline to 72 when the last switch to Truvada took place; 25 participants switched to Truvada from the "maintain baseline regimen" group in Study Phase 2).
|
|---|---|---|---|
|
Infections and infestations
Bronchitis
|
6.4%
3/47
|
4.4%
2/45
|
4.2%
3/72
|
|
Infections and infestations
Herpes simplex
|
6.4%
3/47
|
0.00%
0/45
|
4.2%
3/72
|
|
Infections and infestations
Nasopharyngitis
|
6.4%
3/47
|
0.00%
0/45
|
4.2%
3/72
|
|
Gastrointestinal disorders
Diarrhoea
|
12.8%
6/47
|
4.4%
2/45
|
9.7%
7/72
|
|
Gastrointestinal disorders
Abdominal pain
|
6.4%
3/47
|
2.2%
1/45
|
4.2%
3/72
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
6.4%
3/47
|
2.2%
1/45
|
4.2%
3/72
|
|
Renal and urinary disorders
Pollakiuria
|
6.4%
3/47
|
0.00%
0/45
|
4.2%
3/72
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead Sciences, investigators in this study may communicate, orally present, or publish in scientific journals or other scholarly media only after the following conditions have been met: results of the study in their entirety have been publicly disclosed by or with the consent of Gilead Sciences in an abstract, manuscript, or presentation form; or study has been completed at all study sites for at least 2 years.
- Publication restrictions are in place
Restriction type: OTHER