Changes in Lipids and Safety of Raltegravir in HIV+ Patients With Hyperlipidemia While on Current Standard Therapy

• Sponsor: The Miriam Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00887653
• Collaborator: Tufts Medical Center (Other), Merck Sharp & Dohme LLC (Industry)
• Enrollment: 20
• Locations: 2
• Arm: 1
• Duration (Months): 59
• Patients Per Site: 10
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The success of combination antiretroviral therapy heralded a revolution in the treatment of HIV in the mid-1990s. However, severe treatment-associated side effects have been observed including diabetes and increased cholesterol which are linked to premature heart attacks. This effect has been described among many regimens containing protease inhibitors (PIs), as well as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Raltegravir is a new medicine which has been shown to be potent and efficacious in suppression of the HIV. This study hopes to determine if switching from a PI or NNRTI to raltegravir will decrease cholesterol in subjects with high cholesterol and well controlled HIV. In addition, the study aims to confirm that raltegravir is safe and well tolerated. It also seeks to confirm if raltegravir will have similar anti-HIV activity compared with the patient's previous regimen.

The study will last 6 months and will involve 20 subjects. HIV-1 infected men and women on PIs or NNRTIs for at least 12 months before study entry with well controlled HIV will be recruited.

Hypotheses:

1. Patients with elevated lipid levels while on combination antiretroviral therapy with PIs or NNRTIs will experience an improvement in lipid levels after switching their PI or NNRTI to a raltegravir based regimen.

2. Raltegravir will be safe and well tolerated.

3. Raltegravir will have similar antiretroviral activity compared with the prior regimen.

Primary Objective:

To demonstrate an improvement in lipid profile (triglycerides or LDL) in subjects switched to raltegravir from PIs or NNRTIs at 2, 3, and 6 months after study entry.

Study Design: Subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily. Those who consent, will receive raltegravir provided by the study for 6 months. At entry, the subjects will undergo a complete physical exam and thereafter targeted exams at each visit. Labs will be drawn as part of clinical care at 2, 3, and 6 months. Some of the blood will be stored for later analysis. Also, the subjects will answer regular surveys on drug toxicity and quality of life. Their cholesterol level will be compared before and after the study. At the end of the study, the participants may choose to continue on raltegravir if they desire.

Condition or Disease	Intervention/Treatment	Phase
HIV; Hyperlipidemia; Hypertriglyceridemia; HIV Infections	Drug: raltegravir	Phase 3

Detailed Description

The success of combination antiretroviral therapy heralded a revolution in the management of patients with HIV in the mid-1990s. Increasingly, severe treatment-associated metabolic side effects have been observed and linked to premature coronary artery disease. This effect has been described among many regimens containing protease inhibitors (PIs) as well as non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Raltegravir is a novel HIV-1 integrase inhibitor which in a comparison study with efavirenz has been shown to be potent and efficacious in suppression of the HIV-1. Minimal side effects were reported which mainly included nausea, headache, dizziness, diarrhea, and insomnia.

Hypotheses:

1. Patients with elevated lipid levels while on combination antiretroviral therapy with PIs or NNRTIs will experience an improvement in lipid levels after switching their PI or NNRTI to a raltegravir based regimen.

2. Raltegravir will be safe and well tolerated.

3. Raltegravir will have similar antiretroviral activity compared with the prior regimen.

Primary Objective:

To demonstrate an improvement in triglycerides or LDL in subjects switched to raltegravir from PIs or NNRTIs at 2 months, 3 months, and 6 months after study entry.

Secondary Objectives:

To assess the immunologic and virologic outcomes in subjects switched to raltegravir from PIs or NNRTIs at 2, 3, and 6 months after entry.

Study Design:

This will be a single arm study where subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily.

Primary endpoint: Change from baseline LDL and change from baseline triglycerides at 3 months, adjusted for BMI and smoking status.

The subjects' plasma viral load before and after switching will be compared with a paired t test at each time point.

The subjects' CD4+ T cell count will be compared with a paired t test before and after switching.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Changes in Lipid Profiles and Safety of Raltegravir Based Antiretroviral Therapy in HIV-1-infected Patients With Hyperlipidemia While on Current Standard Therapy
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Raltegravir This is a single arm study where HIV-infected individuals virologically suppressed on current regimen will be switched to raltegravir +optimized back ground regimen for 6 months	Drug: raltegravir; This will be a single arm study where subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily.; Other Names: Isentress

Outcome Measures

Primary Outcome Measures

1. Change From Baseline Triglycerides [3 months]

   Assess changes from baseline triglycerides at 3 months

2. Change From Baseline Triglycerides [6 months]

   Assess changes from baseline triglycerides at 6 months

Secondary Outcome Measures

1. Proportion of Patients With Plasma Viral Load Below the Limit of Detection [6 months]

   Assess proportion of patients with PVL below limit of detection at end of study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age >18

• Fasting LDL>130 mg/dL

• Fasting triglycerides >250 mg/dL

• Plasma viral load below 50 copies/mL on current regimen for 6 months prior to study entry.

• No prior history of any NRTI resistance.

Exclusion Criteria:

• History of NRTI resistance mutations

• Need for medications that have drug interactions with raltegravir: dilantin, phenobarbitol and rifampin

• Unstable clinical condition, such as unstable cardiac disease, or cancer requiring ongoing chemotherapy or radiation therapy, or other medical condition which, in the opinion of the investigator, would preclude a subject from safely undergoing study procedures.

• Breast-feeding or pregnancy.

• Use of immunosuppressive medications within 60 days prior to study entry.

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tufts University	Boston	Massachusetts	United States	02111
2	Miriam Hospital Immunology Clinic	Providence	Rhode Island	United States	02906

Sponsors and Collaborators

• The Miriam Hospital
• Tufts Medical Center
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Karen Tashima, MD, The Miriam Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Aadia Rana, Assistant Professor of Medicine, The Miriam Hospital
• ClinicalTrials.gov Identifier: NCT00887653
• Other Study ID Numbers: 2007-09
• First Posted: Apr 24, 2009
• Last Update Posted: Oct 10, 2014
• Last Verified: Oct 1, 2014

• Additional relevant MeSH terms: Hyperlipidemias; Hyperlipoproteinemias; Hypertriglyceridemia; Raltegravir Potassium

Study Results

Participant Flow

Arm/Group Title	Raltegravir Arm
Arm/Group Description	This is a single arm study where HIV-infected individuals virologically suppressed on current regimen will be switched to raltegravir +optimized back ground regimen for 6 months raltegravir: This will be a single arm study where subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily.
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Raltegravir Arm
Arm/Group Description	This is a single arm study where HIV-infected individuals virologically suppressed on current regimen will be switched to raltegravir +optimized back ground regimen for 6 months raltegravir: This will be a single arm study where subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily.
Overall Participants	20
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52
Sex: Female, Male (Count of Participants)
Female	3 15%
Male	17 85%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 10%
White	16 80%
More than one race	0 0%
Unknown or Not Reported	2 10%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline Triglycerides
Description	Assess changes from baseline triglycerides at 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Raltegravir Arm
Arm/Group Description	This is a single arm study where HIV-infected individuals virologically suppressed on current regimen will be switched to raltegravir +optimized back ground regimen for 6 months raltegravir: This will be a single arm study where subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily.
Measure Participants	20
Median (Full Range) [units on a scale]	125

2. Secondary Outcome

Title	Proportion of Patients With Plasma Viral Load Below the Limit of Detection
Description	Assess proportion of patients with PVL below limit of detection at end of study.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

One subject was prematurely discontinued from the study at week 12 due to detectable HIV-1 RNA of 57 copies/mL that was sustained at 61 copies on repeated measurement two weeks later.

Arm/Group Title	Raltegravir Arm
Arm/Group Description	This is a single arm study where HIV-infected individuals virologically suppressed on current regimen will be switched to raltegravir +optimized back ground regimen for 6 months raltegravir: This will be a single arm study where subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily.
Measure Participants	20
Number [proportion of participants]	0 0%

3. Primary Outcome

Title	Change From Baseline Triglycerides
Description	Assess changes from baseline triglycerides at 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Raltegravir Arm
Arm/Group Description	This is a single arm study where HIV-infected individuals virologically suppressed on current regimen will be switched to raltegravir +optimized back ground regimen for 6 months raltegravir: This will be a single arm study where subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily.
Measure Participants	20
Median (Full Range) [units on a scale]	120

Adverse Events

Arm/Group Title	Raltegravir Arm
Arm/Group Description	This is a single arm study where HIV-infected individuals virologically suppressed on current regimen will be switched to raltegravir +optimized back ground regimen for 6 months raltegravir: This will be a single arm study where subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily.
All Cause Mortality
	Raltegravir Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Raltegravir Arm
	Affected / at Risk (%)	# Events
Total	1/20 (5%)
Immune system disorders
Virologic Failure	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Raltegravir Arm
	Affected / at Risk (%)	# Events
Total	0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

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.