Lopinavir/r or Fosamprenavir/r Switch to Atazanavir/r or Darunavir/r (LARD)

This study has been completed.

Sponsor:

Collaborator:

Tibotec Pharmaceutical Limited

Information provided by (Responsible Party):

Daniel Skiest, MD, Community Research Initiative of New England

ClinicalTrials.gov Identifier:

NCT00756730

First received: September 18, 2008

Last updated: October 23, 2012

Last verified: October 2012

History of Changes

Results First Received: February 21, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	HIV Infections
Interventions:	Drug: ATV/r Drug: DRV/r

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r

Participant Flow: Overall Study

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD
STARTED	25	24
COMPLETED	25	22
NOT COMPLETED	0	2
discontinued due to rash prior to week 4	0	1
persistent low-level viremmia	0	1

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r
Total	Total of all reporting groups

Baseline Measures

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Total
Number of Participants [units: participants]	25	24	49
Age, Customized [units: years] Mean ( Full Range )	48 ( 34 to 67 )	46 ( 30 to 60 )	47 ( 30 to 67 )
Gender [units: participants]
Female	2	2	4
Male	23	22	45
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	7	12	19
Not Hispanic or Latino	18	11	29
Unknown or Not Reported	0	1	1
Region of Enrollment [units: participants]
United States	25	24	49
CD4 Count [units: cells/mm3] Mean ( Full Range )	584 ( 249 to 996 )	554 ( 31 to 1066 )	569 ( 31 to 1066 )
Viral Load [units: copies/mL]	NA ^[1]	NA ^[1]	0
Baseline antiretroviral medications - Protease inhibitors [units: participants]
Lopinavir/ritonavir (LPV/r)	23	23	46
fosamprenavir/ritonavir (FPV/r)	2	1	3
Baseline medications - Nucleoside analogs [units: Participants]
viread (TDF)/emtriva (FTC)	15	17	32
ziagen (ABC)/Epivir (3TC)	5	5	10
other	5	2	7
Lipid Lowering Medications [units: participants]
statin	6	3	9
fibrate	5	6	11
fish oil	5	3	8
niacin	0	1	1
none	9	11	20

[1]	VL was not detected. All values were reported less than 50 copies/ml, the lower limit of detection.

Outcome Measures

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1. Primary:

Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24. [ Time Frame: baseline, 24 weeks ]

Measure Type	Primary
Measure Title	Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24.
Measure Description	A 10% decline in triglycerides (TGs) was determined to be clinically significant. The percentage of people that experienced a 10% decline was calculated by dividing the number who had a decline of 10% TGs by the total number of participants in the arm.
Time Frame	baseline, 24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia. Neither subject met criteria for virologic failure.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r

Measured Values

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD
Number of Participants Analyzed [units: participants]	25	22
Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24. [units: percentage of patients]	80	73

No statistical analysis provided for Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24.

2. Primary:

At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL [ Time Frame: 24 weeks ]

Measure Type	Primary
Measure Title	At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL
Measure Description	No text entered.
Time Frame	24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r

Measured Values

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD
Number of Participants Analyzed [units: participants]	25	22
At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL [units: percentage of participants]	48	55

No statistical analysis provided for At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL

3. Primary:

The Change in Fasting Triglyceride Level From Baseline to Week 24 [ Time Frame: Baseline to week 24 ]

Measure Type	Primary
Measure Title	The Change in Fasting Triglyceride Level From Baseline to Week 24
Measure Description	No text entered.
Time Frame	Baseline to week 24
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r

Measured Values

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD
Number of Participants Analyzed [units: participants]	25	22
The Change in Fasting Triglyceride Level From Baseline to Week 24 [units: mg/dL] Mean ( Full Range )	-126 ( -312 to 133 )	-88 ( -469 to 90 )

No statistical analysis provided for The Change in Fasting Triglyceride Level From Baseline to Week 24

4. Secondary:

Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 [ Time Frame: Week 4, 12 & 24 ]

Measure Type	Secondary
Measure Title	Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24
Measure Description	No text entered.
Time Frame	Week 4, 12 & 24
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r

Measured Values

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD
Number of Participants Analyzed [units: participants]	25	24
Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 [units: percentage of participants]
Week 4	100	100
Week 12	100	100
Week 24	100	100

No statistical analysis provided for Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24

5. Secondary:

Difference in CD4 From Baseline to Week 24 [ Time Frame: baseline to Week 24 ]

Measure Type	Secondary
Measure Title	Difference in CD4 From Baseline to Week 24
Measure Description	No text entered.
Time Frame	baseline to Week 24
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r

Measured Values

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD
Number of Participants Analyzed [units: participants]	25	22
Difference in CD4 From Baseline to Week 24 [units: cells/mm^3] Mean ± Standard Error	10.75 ± 17.67	14.28 ± 19.77

No statistical analysis provided for Difference in CD4 From Baseline to Week 24

6. Secondary:

Total Cholesterol in the Two Study Groups at 24 Weeks [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Title	Total Cholesterol in the Two Study Groups at 24 Weeks
Measure Description	No text entered.
Time Frame	Week 24
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r

Measured Values

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD
Number of Participants Analyzed [units: participants]	25	22
Total Cholesterol in the Two Study Groups at 24 Weeks [units: mg/dL] Mean ( Full Range )	195 ( 110 to 311 )	195 ( 132 to 304 )

No statistical analysis provided for Total Cholesterol in the Two Study Groups at 24 Weeks

7. Secondary:

LDL Cholesterol at Week 24 [ Time Frame: week 24 ]

Measure Type	Secondary
Measure Title	LDL Cholesterol at Week 24
Measure Description	No text entered.
Time Frame	week 24
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r

Measured Values

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD
Number of Participants Analyzed [units: participants]	25	22
LDL Cholesterol at Week 24 [units: mg/dL] Mean ( Full Range )	116 ( 55 to 180 )	111 ( 46 to 204 )

No statistical analysis provided for LDL Cholesterol at Week 24

8. Secondary:

HDL Cholesterol at Week 24 [ Time Frame: 24 weeks ]

Measure Type	Secondary
Measure Title	HDL Cholesterol at Week 24
Measure Description	No text entered.
Time Frame	24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.

Reporting Groups

	Description
Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD
Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD	Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r

Measured Values

	Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD	Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD
Number of Participants Analyzed [units: participants]	25	22
HDL Cholesterol at Week 24 [units: mg/dL] Mean ( Full Range )	38 ( 22 to 54 )	40 ( 26 to 55 )

No statistical analysis provided for HDL Cholesterol at Week 24

Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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More Information

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Certain Agreements:

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact:

Name/Title: Dr. Daniel Skiest
Organization: Community Research initiavte
phone: 413 794 5376
e-mail: Daniel.Skiest@baystatehealth.org

No publications provided

Responsible Party:	Daniel Skiest, MD, Community Research Initiative of New England
ClinicalTrials.gov Identifier:	NCT00756730 History of Changes
Other Study ID Numbers:	08-09
Study First Received:	September 18, 2008
Results First Received:	February 21, 2012
Last Updated:	October 23, 2012
Health Authority:	United States: Food and Drug Administration

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