Bone and Body Comp: A Sub Study of the SECOND-LINE Study

• Sponsor: Kirby Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01513122
• Collaborator: (none)
• Enrollment: 210
• Locations: 7
• Arms: 2
• Duration (Months): 42
• Patients Per Site: 30
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The use of anti HIV drugs (ART), and in particular a class of drugs known as nucleoside reverse transcriptase inhibitors (N(t)RTI), has been associated with changes in body fat and in particular loss of peripheral fat in the limbs. Low bone mineral density and osteoporosis are also common in HIV-infected patients. There appears to be some association between ART and bone loss, but this is poorly understood and requires further research. The SECOND-LINE study provides an opportunity to examine if a new anti-HIV drug (raltegravir) can result in greater increase in limb fat than a drug regimen containing N(t)RTI, which is currently standard of care. This study also provides an opportunity to examine if additional bone loss occurs with the second regimen of anti-HIV drugs and whether non-N(t)RTI regimens of ART used in second line therapy result in more or less bone loss than use of other classes of anti-HIV drugs such as protease inhibitors or N(t)RTI combinations.

It is hypothesized that subjects randomised into Raltegravir arm will demonstrate greater increases in limb fat and smaller reductions in bone density at the proximal femur over 48 weeks than those randomised into the control arm (LPV/r + 2-3N(t)RTIs).

Condition or Disease	Intervention/Treatment	Phase
HIV	Drug: Lopinavir / ritonavir; Drug: 2-3N(t)RTI; Drug: raltegravir	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bone and Body Comp: A Sub Study of the SECOND-LINE Study
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTI	Drug: Lopinavir / ritonavir; LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily; Drug: 2-3N(t)RTI
Active Comparator: Arm 2. Lopinavir /ritonavir + raltegravir	Drug: Lopinavir / ritonavir; LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily; Drug: raltegravir; raltegravir 400mg 1 tablet twice daily.

Outcome Measures

Primary Outcome Measures

1. Mean Bone Mineral Density Changes From Baseline to 48 Weeks as Measured by DXA Scan [48 weeks]

2. Mean Limbs Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan [48 weeks]

Secondary Outcome Measures

1. Mean Total Body Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan [48 weeks]

2. Mean Triglycerides Changes From Baseline to 48 Weeks [48 weeks]

3. Mean Total Cholesterol Changes From Baseline to 48 Weeks [48 weeks]

4. Mean Glucose Changes From Baseline to 48 Weeks [48 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Second-Line main study identifier: NCT00931463

Inclusion Criteria:

1. HIV-1 positive by licensed diagnostic test

2. Aged 16 years or older (or minimum age as determined by local regulations or as legal requirements dictate)

3. Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for ≥ 24 weeks

4. No change in antiretroviral therapy within 12 weeks prior to screening

5. Failed first-line NNRTI + 2N(t)RTI combination therapy according to virological criteria defined by two consecutive (≥7 days apart) HIV RNA results of > 500 copies/mL

6. No prior or current exposure to HIV protease inhibitors and/or HIV integrase inhibitors

7. Able to provide written informed consent

Exclusion Criteria:

1. The following laboratory variables:

• absolute neutrophil count (ANC) < 500 cells/µL

• hemoglobin < 7.0 g/dL

• platelet count < 50,000 cells/µL

• ALT > 5 x ULN

1. Pregnant or nursing mothers

2. Participants with active viral hepatitis B infection defined by the presence in serum of hepatitis B surface antigen

3. Use of immunomodulators within 30 days prior to screening

4. Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride, pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine, astemizole, terfenadine, vardenafil, and St. John's wort)

5. Intercurrent illness requiring hospitalisation

6. Active opportunistic disease not under adequate control in the opinion of the site Principal Investigator

7. Participants with current alcohol or illicit substance abuse that in the opinion of the site Principal Investigator might adversely affect participation in the study

8. Participants deemed by the site Principal Investigator unlikely to be able to remain in follow-up for the protocol-defined period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CEADI	Buenos Aires		Argentina
2	YRGCare Medical Centre	Chennai		India	600113
3	University of Malaya Medical Centre	Kuala Lumpur		Malaysia	50603
4	JOSHA Research	Bloemfontein		South Africa
5	Desmond Tutu HIV Foundation	Cape Town		South Africa	7925
6	Chris Hani Baragwanath Hospital	Soweto		South Africa
7	HIV-NAT Program on AIDS - Thai Red Cross	Bangkok		Thailand	10330

Sponsors and Collaborators

• Kirby Institute

Investigators

• Principal Investigator: Paddy Mallon, Mater Misericordiae University Hospital, Dublin
• Principal Investigator: Waldo Belloso, Hospital Italiano, Argentina
• Principal Investigator: Samuel Ferret, Hopital Saint-Louis, France
• Principal Investigator: Praphan Phanuphak, HIV-NAT Program on AIDS - Thai Red Cross, Bangkok
• Principal Investigator: Jennifer Hoy, The Alfred

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kirby Institute
• ClinicalTrials.gov Identifier: NCT01513122
• Other Study ID Numbers: 2L body comp sub-study
• First Posted: Jan 20, 2012
• Last Update Posted: Sep 4, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Ritonavir; Lopinavir; Raltegravir Potassium

Study Results

Participant Flow

Arm/Group Title	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI	Arm 2. Lopinavir /Ritonavir + Raltegravir
Arm/Group Description	Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI	Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.
Period Title: Overall Study
STARTED	102	108
COMPLETED	91	105
NOT COMPLETED	11	3

Baseline Characteristics

Arm/Group Title	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI	Arm 2. Lopinavir /Ritonavir + Raltegravir	Total
Arm/Group Description	Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI	Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.	Total of all reporting groups
Overall Participants	102	108	210
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	38.6 (7.8)	38.9 (7.7)	38.8 (7.8)
Sex: Female, Male (Count of Participants)
Female	47 46.1%	63 58.3%	110 52.4%
Male	55 53.9%	45 41.7%	100 47.6%

Outcome Measures

1. Primary Outcome

Title	Mean Bone Mineral Density Changes From Baseline to 48 Weeks as Measured by DXA Scan
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

97 participants reached week 48 in 2-3N(t)RTI arm. 107 reached week 48 in the RAL arm (1 death)

Arm/Group Title	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI	Arm 2. Lopinavir /Ritonavir + Raltegravir
Arm/Group Description	Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI	Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.
Measure Participants	97	107
Mean (95% Confidence Interval) [percentage change]	-5.2	-2.9

2. Primary Outcome

Title	Mean Limbs Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI	Arm 2. Lopinavir /Ritonavir + Raltegravir
Arm/Group Description	Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI	Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.
Measure Participants	94	107
Mean (95% Confidence Interval) [percentage change]	15.7	21.1

3. Secondary Outcome

Title	Mean Total Body Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI	Arm 2. Lopinavir /Ritonavir + Raltegravir
Arm/Group Description	Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI	Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.
Measure Participants	94	107
Mean (95% Confidence Interval) [kg]	1.4	2.1

4. Secondary Outcome

Title	Mean Triglycerides Changes From Baseline to 48 Weeks
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI	Arm 2. Lopinavir /Ritonavir + Raltegravir
Arm/Group Description	Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI	Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.
Measure Participants	94	105
Mean (95% Confidence Interval) [mmol/L]	0.6	0.8

5. Secondary Outcome

Title	Mean Total Cholesterol Changes From Baseline to 48 Weeks
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI	Arm 2. Lopinavir /Ritonavir + Raltegravir
Arm/Group Description	Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI	Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.
Measure Participants	94	105
Mean (95% Confidence Interval) [mmol/L]	0.4	0.6

6. Secondary Outcome

Title	Mean Glucose Changes From Baseline to 48 Weeks
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI	Arm 2. Lopinavir /Ritonavir + Raltegravir
Arm/Group Description	Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI	Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.
Measure Participants	94	105
Mean (95% Confidence Interval) [mmol/L]	-0.04	-0.1

Adverse Events

Adverse Event Reporting Description	Adverse Events were not planned to be analyzed for the sub-study and that complete adverse event information is included in the main study report (NCT00931463)
Arm/Group Title	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI		Arm 2. Lopinavir /Ritonavir + Raltegravir
Arm/Group Description	Lopinavir / ritonavir + 2-3N(t)RTI: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3 N(t)RTI		Lopinavir /ritonavir + raltegravir: LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400mg 1 tablet twice daily.
All Cause Mortality
	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI		Arm 2. Lopinavir /Ritonavir + Raltegravir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI		Arm 2. Lopinavir /Ritonavir + Raltegravir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Arm 1. Lopinavir / Ritonavir + 2-3N(t)RTI		Arm 2. Lopinavir /Ritonavir + Raltegravir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is a Clinical Trial Agreement signed with each PI detailing the publication policy and disclosure of study's information, in summary: The Institution, its personnel and the Principal Investigator must not Publish or present any aspect of the Study without the prior written approval of the sponsor, except for the purposes of internal training Publications or presentations of results from the Study will follow the agreement's publication/presentation guidelines