Cardiovascular Risk in HIV Patients Switching From a Boosted Protease Inhibitor (PI) to Dolutegravir (DTG)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
St Stephens Aids Trust
ClinicalTrials.gov Identifier:
NCT02098837
First received: March 20, 2014
Last updated: July 26, 2016
Last verified: July 2016
  Purpose

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 Intervention Phase
HIV
Drug: Dolutegravir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by St Stephens Aids Trust:

Primary Outcome Measures:
  • Virological suppression [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Maintenance of virological suppression (ie HIV-1 RNA <50 c/ml) after 48 weeks

  • Total cholesterol [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Change from baseline in total cholesterol at week 48


Secondary Outcome Measures:
  • Virological Suppression [ Time Frame: 24 - 96 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Change in CD4 count from baseline to week 24, 48 and 96

  • Baseline in total cholesterol [ Time Frame: 24 - 96 weeks ] [ Designated as safety issue: Yes ]
    Change from baseline in total cholesterol at weeks 24 and 96

  • Change from baseline to lipid values [ Time Frame: 24 - 96 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Safety (clinical and laboratory adverse events) at weeks 24, 48 and 96

  • Changes in markers of inflammation [ Time Frame: 48 - 96 weeks ] [ Designated as safety issue: Yes ]
    Changes in markers of inflammation at baseline, week 48 and week 96

  • Tolerability [ Time Frame: 24 - 96 weeks ] [ Designated as safety issue: Yes ]
    Tolerability (EuroQoL questionnaire) at weeks 24, 48 and 96

  • Changes in markers of coagulation [ Time Frame: 48 - 96 weeks ] [ Designated as safety issue: Yes ]
    Changes in markers of coagulation at baseline, week 48 and week 96

  • Changes in markers of endothelial dysfunction [ Time Frame: 48 - 96 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Change from baseline to average thickness of common carotid artery walls at weeks 48 and 96


Enrollment: 415
Study Start Date: April 2014
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Immediate switch
Patients will be randomised to switch from a boosted PI to dolutegravir at baseline.
Drug: Dolutegravir
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.
Drug: Dolutegravir
Dolutegravir 50mg once daily
Other Name: Tivicay

Detailed Description:

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)

  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient volunteers who meet all of the following criteria are eligible for this trial:

    1. Is male or female aged over 50, OR aged over 18 years with a Framingham risk score above 10%
    2. Has documented HIV-1 infection
    3. Has signed the Informed Consent Form voluntarily
    4. Is willing to comply with the protocol requirements
    5. Has been receiving an ARV regimen containing a boosted PI (darunavir, atazanavir, lopinavir, or fosamprenavir) plus 2NRTIs for >24 weeks
    6. Has stable virological suppression (plasma HIV-RNA <50 copies/mL for >24 weeks)
    7. If female and of childbearing potential, is using effective birth control methods and is willing to continue practising these birth control methods during the trial and for at least 2 weeks after the last dose of study medication. Note: Non-childbearing potential is defined as either post-menopausal (12 months of spontaneous amenorrhoea and ≥45 years) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy
    8. If a heterosexually active male, he is using effective birth control methods and is willing to continue practising these birth control methods during the trial and until follow-up visit

Exclusion Criteria:

  • Patients meeting 1 or more of the following criteria cannot be selected:

    1. Infected with HIV-2
    2. Using any concomitant therapy disallowed as per the reference safety information and product labelling for the study drugs
    3. Has acute viral hepatitis including, but not limited to, A, B, or C
    4. Has chronic hepatitis B and/or C with AST and/or ALT >5 x ULN Note: Subjects can enter trial with chronic HBV if HBV-DNA undetectable at screen (and no detectable result in last 6 months) and with chronic HCV if not expected to require treatment during the trial period.
    5. Any investigational drug within 30 days prior to the trial drug administration
    6. History of exposure to any ARVs other than PIs or NRTIs except if switch was for tolerability/toxicity (NOTE: patients who have previously taken part in single drug trials for less than 14 days need not be excluded, or for virological failure with a genotypic resistance test without mutations
    7. Any prior evidence of primary viral resistance based on the presence of any major resistance-associated mutation to backbone NRTI
    8. History of prior virological failure,eg 2 consecutive HIV-1 RNA >50 c/ml -at or after week 32 following first ART initiation or confirmed rebound viraemia >200 copies/ml after having a VL of <50 copies/ml without resistance test or with significant mutations to any other ARV regimen (NOTE: Switch for toxicity or tolerability with wild type virus does not count as virological failure)
    9. Dialysis or renal insufficiency (creatinine clearance < 50ml/min)
    10. History of decompensated liver disease (AST or ALT≥5x the upper limit of normal (ULN) or ALT ≥ )3 x ULN and bilirubin ≥ 1.5 x ULN with > 35% direct bilirubin.
    11. Unstable liver disease (as defined by the presence of ascities, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), know biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones))
    12. Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification
    13. If female, currently pregnant or breastfeeding
    14. Opportunistic infection within 4 weeks prior to first dose of DTG
    15. Clinical decision that a switch of antiretroviral therapy should be immediate
    16. Screening blood result with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed).
    17. Any condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the trial.
    18. History or presence of allergy to the study drug or their components
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02098837

Locations
Belgium
Insititute Of Tropical Medicine Antwerp
Antwerp, Belgium, B-2000
CHU Saint-Pierre
Brussels, Belgium, 100
Universitaire Ziekenhuis Gent
Gent, Belgium, 9000
France
Hopital de la Croix Rousse
Lyon, France, 69004
Service des Maladies Infectieuses et Tropicales du CHU de NANTES
Nantes, France, 44093
Hopital Saint Louis
Paris, France, 75010
Pitié-Salpêtrière Hospital
Paris, France, 75013
Hospital Bichat Claude-Bernard
Paris, France, 75018
Germany
Universitätsklinikum Bonn
Bonn, Germany, 53127
Universitätsklinikum Essen
Essen, Germany, 45147
Klinikum der Goethe-Universität Frankfurt
Frankfurt, Germany, 60590
ICH Infektiologisches Centrum Hamburg
Hamburg, Germany, 20146
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Italy
Santa Maria Annunziata di Firenze
Antella-Firenze, Firenze, Italy, 50011
San Paolo Hospital
Milan, Italy, 20142
Azienda Ospedaliera - Polo Universitario 'Luigi Sacco'
Milan, Italy, 20157
Universitaria di Modena
Modena, Italy, 41124
Spain
Universitario Alicante
Alicante, Spain, 03010
Hospital General Universitario de Elche
Alicante, Spain, 03203
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Clinic Barcelona
Barcelona, Spain, 08036
Universitari de Bellvitge
Barcelona, Spain, 08907
IrsiCaixa
Barcelona, Spain, 08916
Hospital Ramon y Cajal
Madrid, Spain, 28034
Hospital Universitario La Paz
Madrid, Spain, 28046
United Kingdom
Elton John Centre
Brighton, United Kingdom, BN2 1ES
Southmead Hospital
Bristol, United Kingdom, BS10 5NB
Bart's Hospital
London, United Kingdom, E1 1BB
Royal Free Hospital
London, United Kingdom, NW3 2QG
St Thomas Hospital
London, United Kingdom, SE1 7EH
Chelsea & Westminster Hospital
London, United Kingdom, Sw10 9NH
St Mary's Hospital
London, United Kingdom, W2 1NY
Mortimer Market Centre
London, United Kingdom, WC1E 6JB
Sponsors and Collaborators
St Stephens Aids Trust
Investigators
Principal Investigator: Jose Gatell, Dr Spanish healthcare system
  More Information

Responsible Party: St Stephens Aids Trust
ClinicalTrials.gov Identifier: NCT02098837     History of Changes
Other Study ID Numbers: NEAT 22/SSAT 060 
Study First Received: March 20, 2014
Last Updated: July 26, 2016
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by St Stephens Aids Trust:
HIV

Additional relevant MeSH terms:
Protease Inhibitors
Dolutegravir
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
HIV Integrase Inhibitors
Integrase Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 25, 2016