Back to resultsA Study to Compare Brachial Artery Reactivity and Cardiovascular Risk of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg Versus a Triple Combination Therapy Containing DRV/r in HIV-1 Infected Patients (MONARCH)
Primary Purpose
Human Immunodeficiency Virus 1
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Darunavir(DRV)
Ritonavir
2 nucleoside reverse transcriptase inhibitors (NRTIs)
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus 1 focused on measuring Human immunodeficiency virus 1, Acquired immunodeficiency syndrome, Immunologic deficiency syndrome, Darunavir/ritonavir, Darunavir, Ritonavir, Nucleoside reverse transcriptase inhibitors (NRTIs), Prezista
Eligibility Criteria
Inclusion Criteria: - Human immunodeficiency virus-1 (HIV-1) infected participants on their first-line treatment with highly active antiretroviral therapy (HAART) (combination of 2 or 3 nucleoside reverse transcriptase inhibitors [NRTIs] with at least 1 additional antiretroviral [ARV] from the non-nucleoside reverse transcriptase inhibitor [NNRTI] and/or protease inhibitors [PI] class) for at least 24 weeks, provided the same ARV combination for at least 8 weeks before screening
- Participants' preference for a more convenient regimen and/or any current or history of toxicity on actual regimen
- Plasma HIV-1 ribonucleic acid (RNA) less than 50 cp/ml for at least 24 weeks before screening, where single viral blips of more than 50 copies/mL are allowed
- Cluster of differentiation 4 (CD4) count more than 100/mm3 at the start of HAART and more than 200/mm3 at screening
- Healthy on the basis of physical examination, medical history, vital signs, clinical laboratory tests, and 12-lead electrocardiogram performed at screening
- Agrees to protocol-defined use of effective contraception
- Postmenopausal, surgically sterile, or abstinent female participants
Exclusion Criteria:
- History of coronary heart disease, uncontrolled hypertension, peripheral vascular disease and or cerebrovascular disease
- History of virological failure on highly active antiretroviral therapy, plasma HIV-1 ribonucleic acid more than 500 copies/mL after initial full virological suppression while on ARV therapy and any PI mutations
- Participants with significantly hepatic and liver insufficiency or diagnosed with acute viral hepatitis or have active clinically significant diseases and acquired immune deficiency syndrome (AIDS) defining illness at screening
- Current significant tobacco use, active drug or alcohol use or dependence
- Use of lipid-lowering drugs within 4 weeks prior to study entry and use of testosterone, anabolic steroids, oral contraceptives or hormonal replacement within 12 weeks prior to study entry or previous or current use of darunavir
- Use of systemic glucocorticoids, long-acting inhaled steroids (inhaled via mouth or nose), or other immunomodulators within 30 days prior to study entry
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Monotherapy
Combination therapy
Arm Description
Monotherapy: darunavir/ritonavir (DRV/r) will be administered for 48 weeks.
DRV/r along with 2 nucleoside reverse transcriptase inhibitors (NRTIs) will be administered for 48 weeks and whenever possible, participants should take these medications at the same time. Switch of NRTIs will be allowed in the event of suspected toxicity/intolerance, providing this change can be linked to a documented adverse event (AE)/serious AE.
Outcomes
Primary Outcome Measures
Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%)
Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter.
Secondary Outcome Measures
Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%)
Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter.
Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL
Change From Baseline to Week 48 in Circulating Endothelial Cells
Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells
Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL
Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL
Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides
Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
The Homeostatic Model Assessment (HOMA) is a method used to quantify insulin resistance and beta-cell function. HOMA-IR is reflected in the diminished effect of insulin on hepatic glucose production. HOMA-IR is calculated as: (Glucose [mg/dL] X Insulin [pmol/L]) / (405 X 6.945). Higher scores indicate worse insulin resistance.
Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score
The Framingham Risk Score is used to estimate the 10-year cardiovascular risk of a participant. It is calculated according to age, laboratory values of total cholesterol and HDL cholesterol, smoking status, and systolic blood pressure. The framingham risk score is calculated as: for males: 0 point (1 percentage) up to 17 points (30 percentages); whereas for females: 0 to 9 points (1 percentage) up to 25 points (30 percentage). Higher scores indicate high cardiovascular risk.
Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total)
Leg fat content will be analyzed by Dual Energy X-ray Absortiometry (DEXA scan).
Change From Baseline to Week 48 in Visceral Fat Content in Abdomen: Median Change in Visceral Abdominal Tissue (VAT)
Visceral fat content in abdomen will be analyzed with median change in VAT by an abdomen Computerized Tomography.
Change From Baseline to Week 48 in Femoral Neck T Score: Median Change in Femoral Neck T Score
T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density.
Change From Baseline to Week 48 in Femoral Neck Z Score: Median Change in Femoral Neck Z Score
Z score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. Z score is the number of standard deviations above or below the mean for the participant's age, sex and ethnicity. This score is calculated from participant's age, gender and race and skeletal site. Z score has a mean of '0' and a standard deviation of '1'. Z score lower than its mean indicate low bone mineral density.
Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score
T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density.
Change From Baseline to Week 48 in Lumbar Z Score: Median Change in Lumbar Z Score
Z score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. Z score is the number of standard deviations above or below the mean for the participant's age, sex and ethnicity. This score is calculated from participant's age, gender and race and skeletal site. Z score has a mean of '0' and a standard deviation of '1'. Z score lower than its mean indicate low bone mineral density.
Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01391013
Brief Title
A Study to Compare Brachial Artery Reactivity and Cardiovascular Risk of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg Versus a Triple Combination Therapy Containing DRV/r in HIV-1 Infected Patients
Acronym
MONARCH
Official Title
A Randomised, Controlled, Open-Label Trial to Compare Brachial Artery Reactivity and Cardiovascular Risk of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg O.D. Versus a Triple Combination Therapy Containing DRV/r in HIV-1 Infected Subjects With Undetectable Plasma HIV-1 RNA on Their Current Treatments.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen-Cilag S.p.A.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to compare change of brachial artery flow mediated vasodilatation using Darunavir/Ritonavir (DRV/r) 800/100 mg once daily as a monotherapy (use of a single medication) versus a triple combination therapy containing 2 nucleoside reverse transcriptase inhibitors (NRTIs) and DRV/r in Human immunodeficiency virus-1 (HIV-1) infected participants.
Detailed Description
This is a Phase II, randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), controlled, single centre study. The study consists of 3 phases including, the screening phase (4 weeks before administration of study medication), treatment phase (48 weeks), and the follow-up phase (4 weeks). In the treatment phase, HIV-infected participants who have not changed their first-line treatment of highly active antiretroviral therapy (HAART) for at least 8 weeks and have documented evidence of their HIV- ribonucleic acid (RNA) measurements being virologically suppressed (HIV-RNA less than 50 copies/mL) for at least 24 weeks prior to the screening, will be randomly assigned equally in two treatment arms: triple combination therapy arm (DRV/r 800/100 mg once daily plus 2 NRTIs) or monotherapy arm (DRV/r 800/100 mg once daily). Participants in the triple combination arm who are already on 2 NRTIs prior to randomization may remain on these or switch them at baseline, where the participants on the monotherapy arm will discontinue HAART at baseline and will start DRV/r 800/100 mg once daily. Safety evaluations will include assessment of adverse events, significant vital signs, and significant laboratory tests. The total duration of the study will be 56 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus 1
Keywords
Human immunodeficiency virus 1, Acquired immunodeficiency syndrome, Immunologic deficiency syndrome, Darunavir/ritonavir, Darunavir, Ritonavir, Nucleoside reverse transcriptase inhibitors (NRTIs), Prezista
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Monotherapy
Arm Type
Experimental
Arm Description
Monotherapy: darunavir/ritonavir (DRV/r) will be administered for 48 weeks.
Arm Title
Combination therapy
Arm Type
Experimental
Arm Description
DRV/r along with 2 nucleoside reverse transcriptase inhibitors (NRTIs) will be administered for 48 weeks and whenever possible, participants should take these medications at the same time. Switch of NRTIs will be allowed in the event of suspected toxicity/intolerance, providing this change can be linked to a documented adverse event (AE)/serious AE.
Intervention Type
Drug
Intervention Name(s)
Darunavir(DRV)
Other Intervention Name(s)
Prezista
Intervention Description
Oral administration of tablet DRV 800 mg (2 tablets of 400 mg) once daily at the same time, within 30 minutes after food for 48 weeks
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
Oral administration of tablet ritonavir 100 mg once daily at the same time, within 30 minutes after food for 48 weeks
Intervention Type
Drug
Intervention Name(s)
2 nucleoside reverse transcriptase inhibitors (NRTIs)
Intervention Description
2 NRTIs will be administered as per the package inserts.
Primary Outcome Measure Information:
Title
Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%)
Description
Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter.
Time Frame
Baseline (Day 1 of Week 1) to Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%)
Description
Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter.
Time Frame
Baseline to Week 48
Title
Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL
Time Frame
Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up (Week 52)
Title
Change From Baseline to Week 48 in Circulating Endothelial Cells
Time Frame
Baseline to Week 48
Title
Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells
Time Frame
Baseline to Week 48
Title
Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL
Time Frame
Baseline (Day1 of Week 1), Week 24, and Week 48
Title
Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL
Time Frame
Baseline, Week 24, and Week 48
Title
Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides
Time Frame
Baseline, Week 24, and Week 48
Title
Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Description
The Homeostatic Model Assessment (HOMA) is a method used to quantify insulin resistance and beta-cell function. HOMA-IR is reflected in the diminished effect of insulin on hepatic glucose production. HOMA-IR is calculated as: (Glucose [mg/dL] X Insulin [pmol/L]) / (405 X 6.945). Higher scores indicate worse insulin resistance.
Time Frame
Baseline, Week 24, and Week 48
Title
Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score
Description
The Framingham Risk Score is used to estimate the 10-year cardiovascular risk of a participant. It is calculated according to age, laboratory values of total cholesterol and HDL cholesterol, smoking status, and systolic blood pressure. The framingham risk score is calculated as: for males: 0 point (1 percentage) up to 17 points (30 percentages); whereas for females: 0 to 9 points (1 percentage) up to 25 points (30 percentage). Higher scores indicate high cardiovascular risk.
Time Frame
Baseline, Week 24, and Week 48
Title
Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total)
Description
Leg fat content will be analyzed by Dual Energy X-ray Absortiometry (DEXA scan).
Time Frame
Baseline to Week 48
Title
Change From Baseline to Week 48 in Visceral Fat Content in Abdomen: Median Change in Visceral Abdominal Tissue (VAT)
Description
Visceral fat content in abdomen will be analyzed with median change in VAT by an abdomen Computerized Tomography.
Time Frame
Baseline to Week 48
Title
Change From Baseline to Week 48 in Femoral Neck T Score: Median Change in Femoral Neck T Score
Description
T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density.
Time Frame
Baseline to Week 48
Title
Change From Baseline to Week 48 in Femoral Neck Z Score: Median Change in Femoral Neck Z Score
Description
Z score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. Z score is the number of standard deviations above or below the mean for the participant's age, sex and ethnicity. This score is calculated from participant's age, gender and race and skeletal site. Z score has a mean of '0' and a standard deviation of '1'. Z score lower than its mean indicate low bone mineral density.
Time Frame
Baseline to Week 48
Title
Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score
Description
T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density.
Time Frame
Baseline to Week 48
Title
Change From Baseline to Week 48 in Lumbar Z Score: Median Change in Lumbar Z Score
Description
Z score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. Z score is the number of standard deviations above or below the mean for the participant's age, sex and ethnicity. This score is calculated from participant's age, gender and race and skeletal site. Z score has a mean of '0' and a standard deviation of '1'. Z score lower than its mean indicate low bone mineral density.
Time Frame
Baseline to Week 48
Title
Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48
Time Frame
Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up (Week 52)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Human immunodeficiency virus-1 (HIV-1) infected participants on their first-line treatment with highly active antiretroviral therapy (HAART) (combination of 2 or 3 nucleoside reverse transcriptase inhibitors [NRTIs] with at least 1 additional antiretroviral [ARV] from the non-nucleoside reverse transcriptase inhibitor [NNRTI] and/or protease inhibitors [PI] class) for at least 24 weeks, provided the same ARV combination for at least 8 weeks before screening
Participants' preference for a more convenient regimen and/or any current or history of toxicity on actual regimen
Plasma HIV-1 ribonucleic acid (RNA) less than 50 cp/ml for at least 24 weeks before screening, where single viral blips of more than 50 copies/mL are allowed
Cluster of differentiation 4 (CD4) count more than 100/mm3 at the start of HAART and more than 200/mm3 at screening
Healthy on the basis of physical examination, medical history, vital signs, clinical laboratory tests, and 12-lead electrocardiogram performed at screening
Agrees to protocol-defined use of effective contraception
Postmenopausal, surgically sterile, or abstinent female participants
Exclusion Criteria:
History of coronary heart disease, uncontrolled hypertension, peripheral vascular disease and or cerebrovascular disease
History of virological failure on highly active antiretroviral therapy, plasma HIV-1 ribonucleic acid more than 500 copies/mL after initial full virological suppression while on ARV therapy and any PI mutations
Participants with significantly hepatic and liver insufficiency or diagnosed with acute viral hepatitis or have active clinically significant diseases and acquired immune deficiency syndrome (AIDS) defining illness at screening
Current significant tobacco use, active drug or alcohol use or dependence
Use of lipid-lowering drugs within 4 weeks prior to study entry and use of testosterone, anabolic steroids, oral contraceptives or hormonal replacement within 12 weeks prior to study entry or previous or current use of darunavir
Use of systemic glucocorticoids, long-acting inhaled steroids (inhaled via mouth or nose), or other immunomodulators within 30 days prior to study entry
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen-Cilag S.p.A. Clinical Trial
Organizational Affiliation
Janssen-Cilag S.p.A.
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
A Study to Compare Brachial Artery Reactivity and Cardiovascular Risk of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg Versus a Triple Combination Therapy Containing DRV/r in HIV-1 Infected Patients
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