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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by St Stephens Aids Trust
Sponsor:
Information provided by (Responsible Party):
St Stephens Aids Trust
ClinicalTrials.gov Identifier:
NCT02098837
First received: March 20, 2014
Last updated: March 25, 2014
Last verified: March 2014
  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


Estimated Enrollment: 420
Study Start Date: April 2014
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (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

  Eligibility

Ages Eligible for Study:   18 Years and older
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, esophagael or gastic 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

Contacts
Contact: Alice Shields 02033156101 alice.shields@chelwest.nhs.uk

Locations
Belgium
Insititute Of Tropical Medicine Antwerp Not yet recruiting
Antwerp, Belgium, B-2000
Contact: Lida van Peterson       lvpetersen@itg.be   
Principal Investigator: Eric Florence, Dr         
CHU Saint-Pierre Not yet recruiting
Brussels, Belgium, 100
Contact: Kabamba Kabeya       infectiousdiseases@stpierre-bru.be   
Principal Investigator: Nathan Clumeck, Dr         
Universitaire Ziekenhuis Gent Not yet recruiting
Gent, Belgium, 9000
Contact: Tessa James       tessa.james@ugent.be   
Principal Investigator: Linos Vandekerckhove, Dr         
France
Hopital de la Croix Rousse Not yet recruiting
Lyon, France, 69004
Contact: Corinne Brochier       corinne.brochier@chu-lyon.fr   
Principal Investigator: Laurent Cotte, Dr         
Service des Maladies Infectieuses et Tropicales du CHU de NANTES Not yet recruiting
Nantes, France, 44093
Contact: Herve Hue       herve.hue@che-nantes.fr   
Principal Investigator: Francois Raffi, Dr         
Hospital Bichat Claude-Bernard Not yet recruiting
Paris, France, 75018
Contact: Sylvie Le Gac       sylvie.legac@bch.aphp.fr   
Principal Investigator: Patrick Yeni, Dr         
Pitié-Salpêtrière Hospital Not yet recruiting
Paris, France, 75013
Contact: Yasmine Dudoit       yasminedudois@psl.aphp.fr   
Principal Investigator: Christine Katlama, Dr         
Hopital Saint Louis Not yet recruiting
Paris, France, 75010
Contact: Samuel Ferret       samuel.ferret@sls.aphp.fr   
Principal Investigator: Jean-Michel Molina, Dr         
Spain
Hospital General Universitario de Elche Not yet recruiting
Alicante, Spain, 03203
Contact: Federico Carlos       f.carlosmenarquez@gmail.com   
Principal Investigator: Felix Gutierrez, Dr         
Universitario Alicante Not yet recruiting
Alicante, Spain, 03010
Contact: Livia Giner       livginer@gmail.com   
Principal Investigator: Joaquin Portillo, Dr         
IrsiCaixa Not yet recruiting
Barcelona, Spain, 08916
Contact: Jordi Puig       j.puig@flsida.org   
Principal Investigator: Bonaventura Clotet, Dr         
Universitari de Bellvitge Not yet recruiting
Barcelona, Spain, 08907
Contact: Nerea Rozas       nrozas@bellvitgehospital.cat   
Principal Investigator: Daniel Podzamczer, Dr         
Hospital Clinic Barcelona Not yet recruiting
Barcelona, Spain, 08036
Contact: Pilar Callau       pcallau@clinic.ub.es   
Principal Investigator: Jose Gatell, Dr         
Hospital de la Santa Creu i Sant Pau Not yet recruiting
Barcelona, Spain, 08025
Contact: Jessica Rodriguez         
Principal Investigator: Pere Domingo, Dr         
Hospital Ramon y Cajal Not yet recruiting
Madrid, Spain, 28034
Contact: Angel Lamas       alm.lamas@gmail.com   
Principal Investigator: Jose Casado, Dr         
Hospital Universitario La Paz Not yet recruiting
Madrid, Spain, 28046
Contact: Juan Miguel       juanmi.castro@gmail.com   
Principal Investigator: Juan Gonzalez, Dr         
United Kingdom
Elton John Centre Not yet recruiting
Brighton, United Kingdom, BN2 1ES
Contact: Nicky Perry       nicky.perry@bsuh.nhs.uk   
Principal Investigator: Martin Fisher, Dr         
Southmead Hospital Not yet recruiting
Bristol, United Kingdom, BS10 5NB
Contact: Louise Jennings       louise.jennings@nbt.nhs.uk   
Principal Investigator: Mark Gompels, Dr         
Mortimer Market Centre Not yet recruiting
London, United Kingdom, WC1E 6JB
Contact: Ana Milinkovic       a.milinkovic@ucl.ac.uk   
Principal Investigator: Laura Waters, Dr         
St Mary's Hospital Not yet recruiting
London, United Kingdom, W2 1NY
Contact: Ken Legg       k.legg@imperial.ac.uk   
Principal Investigator: Alan Winston, Dr         
Chelsea & Westminster Hospital Not yet recruiting
London, United Kingdom, Sw10 9NH
Contact: Alice Shields    02033156101    alice.shields@chelwest.nhs.uk   
Principal Investigator: Graeme Moyle, Dr         
Bart's Hospital Not yet recruiting
London, United Kingdom, E1 1BB
Contact: James Hand       james.hand@bartshealth.nhs.uk   
Principal Investigator: Chloe Orkin, Dr         
Royal Free Hospital Not yet recruiting
London, United Kingdom, NW3 2QG
Contact: Anne Carroll       anne.carroll2@nhs.net   
Principal Investigator: Margaret Johnson, Dr         
St Thomas Hospital Not yet recruiting
London, United Kingdom, SE1 7EH
Contact: Alice Sharp       alice.sharp@kcl.ac.uk   
Principal Investigator: Julie Fox, Dr         
Sponsors and Collaborators
St Stephens Aids Trust
Investigators
Principal Investigator: Jose Gatell, Dr Spanish healthcare system
  More Information

No publications provided

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: March 25, 2014
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

Keywords provided by St Stephens Aids Trust:
HIV

Additional relevant MeSH terms:
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014