Cardiovascular Risk in HIV Patients Switching From a Boosted Protease Inhibitor (PI) to Dolutegravir (DTG)
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|ClinicalTrials.gov Identifier: NCT02098837|
Recruitment Status : Completed
First Posted : March 28, 2014
Last Update Posted : April 9, 2018
The purpose of the study is to investigate the benefits of switching away from a kind of drug called a boosted protease inhibitor (PI) to a new drug called dolutegravir on patients' cardiovascular health (the health of their hearts). Patients are currently taking two other anti-HIV drugs, called nucleoside reverse transcriptase inhibitors (NRTIs), with their boosted PIs; these NRTIs will not be changed throughout the study. In order to compare the boosted PI and dolutegravir more accurately, half of study participants will be switched to dolutegravir immediately, and the other half will be switched after 48 weeks of continuing on the boosted PI.
Boosted PIs are associated with increased heart and circulation risk so it is hoped that switching from a boosted PI to dolutegravir will improve the health of the patients' hearts. Dolutegravir is a drug for HIV treatment which has been approved for use in HIV patients in the US and Europe. Clinical trials using dolutegravir have found that it is effective at suppressing the HIV virus, and it is at least as effective as the other drugs.
This study will also investigate the safety (in terms of other side effects and the routine blood tests which the investigators ordinarily use to monitor patients' treatment) and monitor effectiveness, patients' viral load and CD4 counts, when patients switch treatment from a boosted PI to dolutegravir. Viral load is the amount of the HIV virus they have in their blood, and CD4 count is a measure of a type of cell that is in their immune system. We also aim to improve patients' cardiovascular health in general by providing them with information on how to live a healthy lifestyle (eg improving their diet, stopping smoking etc).
|Condition or disease||Intervention/treatment||Phase|
|HIV||Drug: Dolutegravir||Phase 4|
Study Design: Randomised, non-inferiority strategic trial over 96 weeks with early or delayed switch from an ARV regimen containing a boosted PI plus 2 NRTIs to dolutegravir (DTG) plus 2 NRTIs in patients having achieved complete virological suppression for more than 24 weeks (HIV-1 RNA <50 c/ml). Patients will be randomised to switch at baseline or at 48 weeks.
Study visits will take place at screening, baseline, weeks 4 (immediate switch group only), 12, 24, 36, 48, 52 (deferred switch group only), 60, 72, 84 and 96, plus a follow up visit 28 days after the last dose of study medication.
Routine investigations will include viral load, CD4, haematology (including haemoglobin, white cell count and differential, platelets), biochemistry (including sodium, potassium, creatinine, albumin, glucose, ALT, ALP, total bilirubin, total cholesterol, HDL, LDL, triglycerides), quality of life questionnaires (EuroQL), urine sample (for haematuria, proteinuria, glycosuria, leukocytes, nitrate & pregnancy test in WOCBP)
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||415 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label Study Examining the Efficacy and Cardiovascular Risk of Immediate Versus Deferred Switch From a Boosted PI to Dolutegravir (DTG) in HIV Infected Patients With Stable Virological Suppression|
|Study Start Date :||April 2014|
|Actual Primary Completion Date :||November 2017|
|Actual Study Completion Date :||December 4, 2017|
Active Comparator: Immediate switch
Patients will be randomised to switch from a boosted PI to dolutegravir at baseline.
Dolutegravir 50mg once daily
Other Name: Tivicay
Active Comparator: Deferred switch
Patients will be randomised to switch from a boosted PI to dolutegravir after 48 weeks.
Dolutegravir 50mg once daily
Other Name: Tivicay
- Virological suppression [ Time Frame: 48 weeks ]Maintenance of virological suppression (ie HIV-1 RNA <50 c/ml) after 48 weeks
- Total cholesterol [ Time Frame: 48 weeks ]Change from baseline in total cholesterol at week 48
- Virological Suppression [ Time Frame: 24 - 96 weeks ]Maintenance of virological suppression (ie HIV-1 RNA <50 c/ml) at week 24 and 96
- CD4 count from baseline [ Time Frame: 24 - 96 weeks ]Change in CD4 count from baseline to week 24, 48 and 96
- Baseline in total cholesterol [ Time Frame: 24 - 96 weeks ]Change from baseline in total cholesterol at weeks 24 and 96
- Change from baseline to lipid values [ Time Frame: 24 - 96 weeks ]Change from baseline to lipid values (LDL, HDL, triglycerides and TC:HDL ratio) and Framingham and DAD scores at weeks 24, 48 and 96
- Safety [ Time Frame: 24 - 96 weeks ]Safety (clinical and laboratory adverse events) at weeks 24, 48 and 96
- Changes in markers of inflammation [ Time Frame: 48 - 96 weeks ]Changes in markers of inflammation at baseline, week 48 and week 96
- Tolerability [ Time Frame: 24 - 96 weeks ]Tolerability (EuroQoL questionnaire) at weeks 24, 48 and 96
- Changes in markers of coagulation [ Time Frame: 48 - 96 weeks ]Changes in markers of coagulation at baseline, week 48 and week 96
- Changes in markers of endothelial dysfunction [ Time Frame: 48 - 96 weeks ]Changes in markers of endothelial dysfunction at baseline, week 48 and week 96
- Change to arterial stiffness augmentation index at weeks 48 and 96 [ Time Frame: 48 - 96 weeks ]Change from baseline to arterial stiffness augmentation index at weeks 48 and 96
- Change to average thickness of common carotid artery walls at weeks 48 and 96 [ Time Frame: 48 - 96 weeks ]Change from baseline to average thickness of common carotid artery walls at weeks 48 and 96
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02098837
|Principal Investigator:||Jose Gatell, Dr||Spanish healthcare system|