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Changes in Weight, Body Composition and Cardiac Risk After Discontinuing Abacavir Treatment in HIV-infected Individuals (AVERTAS-1)

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ClinicalTrials.gov Identifier: NCT04904406
Recruitment Status : Recruiting
First Posted : May 27, 2021
Last Update Posted : May 27, 2021
Sponsor:
Information provided by (Responsible Party):
Thomas Benfield, Hvidovre University Hospital

Brief Summary:

Randomized controlled parallel open-label study in people living with HIV and at least 6 month of treatment with dolutegravir/abacavir/lamivudine prior to inclusion.

Participants (n=95) are randomized to continue 3 drug-regimen dolutegravir/abacavir/lamivudine (control) or switch to two-drug regimen with dolutegravir/lamivudine (intervention). Follow-up is 48 weeks. Data is collected at baseline and week 48. Primary outcome is changes in weight from baseline of more than 2 kg. Secondary outcomes are changes in cardiac risk, composition and calcification of the heart tissue, and changes in body composition and metabolism, inflammation and coagulation. A MRI substudy is applied to focus on the cardiac adverse effects of abacavir.


Condition or disease Intervention/treatment Phase
Hiv HIV Infections HIV Cardiomyopathy Weight Change, Body HIV Lipodystrophy Cardiovascular Diseases Drug: Dolutegravir / Lamivudine Oral Tablet Phase 4

Detailed Description:
In the MRI sub study 40 patients from the main study (20 from each group) are included. A cardiac MRI are performed at baseline and week 48 to evaluate cardiac effects of abacavir.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A randomized controlled open-label superiority trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Changes in Weight and Body Composition After Switch to Dolutegravir/Lamivudine Compared to Continued Dolutegravir/Abacavir/Lamivudine for Virologically Suppressed HIV Infection: A Randomized Open-label Superiority Trial: AVERTAS-1
Actual Study Start Date : October 22, 2020
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: dolutegravir/lamivudine
50 mg dolutegravir and 300 mg lamivudine (co-formulated) once daily for 48 weeks
Drug: Dolutegravir / Lamivudine Oral Tablet
Discontinuing abacavir by switching from three-drug regimen with dolutegravir/abacavir/lamivudine to two-drug regimen with dolutegravir/lamivudine
Other Name: Dolutegravir/abacavir/lamivudine

No Intervention: dolutegravir/abacavir/lamivudine
50 mg dolutegravir, 600 mg abacavir and 300 mg lamivudine (co-formulated) once daily for 48 weeks



Primary Outcome Measures :
  1. Changes in body weight of ≥2 kg [ Time Frame: 48 weeks ]
    Fasting body weight


Secondary Outcome Measures :
  1. Virological control [ Time Frame: 48 weeks ]
    HIV-RNA <50 copies/ml

  2. Changes in self-rated health [ Time Frame: 48 weeks ]
    12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best).

  3. Change in metabolism [ Time Frame: 48 weeks ]
    Impaired insulin resistance and/or β-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

  4. Changes in cardiac risk [ Time Frame: 48 weeks ]
    D:A:D CVD risk score: Five and ten years predicted cardio vascular disease risk (percent)

  5. Changes in carotid artery intima-media thickness (cIMT) [ Time Frame: 48 weeks ]
    Measured by ultrasound.

  6. Changes in Coronary artery calcium score (CACS) [ Time Frame: 48 weeks ]
    Measures by CT-scan. Scores from 0 and with no upper limit. The higher score, the worse calcification/plaque level and higher CVD risk.

  7. Changes in cardiac blood markers [ Time Frame: 48 weeks ]
    Changes in N-terminal pro-B-type natriuretic peptide (Pro-BNP)

  8. Changes in bloodpressure [ Time Frame: 48 weeks ]
    Systolic and diastolic blood pressure (mmHg)

  9. Changes in fat distribution VAT/SAT [ Time Frame: 48 weeks ]

    Measured by CT-scan

    • Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by abdominal CT.


  10. Changes in liver stiffness [ Time Frame: 48 weeks ]
    Measured by CT-scan and liver elastography

  11. Changes in liver fat infiltration [ Time Frame: 48 weeks ]
    Measured by CT-scan and liver elastography

  12. Changes in fat distribution in trunk, limb and extremities [ Time Frame: 48 weeks ]
    Measured by dual energy xray absorptiometry (DEXA)

  13. Changes in inflammation [ Time Frame: 48 weeks ]
    High-sensitive C-reactive protein

  14. Changes in interleukins [ Time Frame: 48 weeks ]
    Interleukin 1- and interleukin 6

  15. Changes in endothelial function [ Time Frame: 48 weeks ]
    Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1

  16. Changes in soluble P-selectin [ Time Frame: 48 weeks ]
    soluble P-selectin

  17. Changes in soluble glycoprotein VI [ Time Frame: 48 weeks ]
    soluble glycoprotein VI

  18. Changes in d-dimer [ Time Frame: 48 weeks ]
    D-dimer

  19. Changes in coagulation [ Time Frame: 48 weeks ]
    Factor 2, 7 and 10 (extrinsic pathway)

  20. Changes in fibrinogen [ Time Frame: 48 weeks ]
    Fibrinogen

  21. Changes in blood Hemoglobin [ Time Frame: 48 weeks ]
    Hemoglobin

  22. Changes in blood platelets [ Time Frame: 48 weeks ]
    Platelets

  23. Changes in plasma creatinine [ Time Frame: 48 weeks ]
    Creatinine

  24. Changes in plasma urea [ Time Frame: 48 weeks ]
    Urea

  25. Changes in plasma sodium [ Time Frame: 48 weeks ]
    Sodium

  26. Changes in plasma potassium [ Time Frame: 48 weeks ]
    Potassium

  27. Changes in plasma bilirubin [ Time Frame: 48 weeks ]
    Bilirubin

  28. Changes in plasma alanine [ Time Frame: 48 weeks ]
    Alanine

  29. Changes in plasma aminotransferase [ Time Frame: 48 weeks ]
    Aminotransferase

  30. Cardiovascular risk [ Time Frame: 48 weeks ]
    Framingham risk score: Estimated 10 years risk of cardiovascular disease (percent)

  31. Cardiac biomarkers [ Time Frame: 48 weeks ]
    Changes in Troponin T (TnT)


Other Outcome Measures:
  1. Cardiac MRI substudy primary outcome (composite) ECV [ Time Frame: 48 weeks ]

    Cardiac MRI applied on 40 patients to evaluate:

    Decrease in extracellular myocardial volume (ECV) from baseline to week 48


  2. Cardiac MRI substudy primary outcome (composite) atrial volume [ Time Frame: 48 weeks ]

    Cardiac MRI applied on 40 patients to evaluate:

    Decrease in left atrial volume from baseline to week 48


  3. Cardiac MRI substudy primary outcome (composite) diastolic function [ Time Frame: 48 weeks ]

    Cardiac MRI applied on 40 patients to evaluate:

    Improvement in diastolic function from baseline to week 48


  4. Cardiac MRI substudy primary outcome (composite) myocardial mass [ Time Frame: 48 weeks ]

    Cardiac MRI applied on 40 patients to evaluate:

    Reduction in myocardial mass from baseline to week 48


  5. Cardiac MRI substudy secondary outcome ejection fraction (EF) [ Time Frame: 48 weeks ]

    Cardiac MRI applied on 40 patients to evaluate:

    Secondary outcomes

    Changes in:

    • Ejection fraction (EF)


  6. Cardiac MRI substudy secondary outcome perfusion [ Time Frame: 48 weeks ]

    Cardiac MRI applied on 40 patients to evaluate:

    Secondary outcomes

    Changes in:

    • Perfusion


  7. Cardiac MRI substudy secondary outcome edema/inflammation [ Time Frame: 48 weeks ]

    Cardiac MRI applied on 40 patients to evaluate:

    Secondary outcomes

    Changes in:

    • Edema/inflammation


  8. Cardiac MRI substudy secondary outcome fibrosis [ Time Frame: 48 weeks ]

    Cardiac MRI applied on 40 patients to evaluate:

    Secondary outcomes

    Changes in:

    • Fibrosis


  9. Cardiac MRI substudy secondary outcome lipid [ Time Frame: 48 weeks ]

    Cardiac MRI applied on 40 patients to evaluate:

    Secondary outcomes

    Changes in:

    • Lipid-water profile Measured by MR spectroscopy




Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 18 years old
  • Diagnosed HIV
  • At least 6 months of ongoing treatment with dolutegravir/ abacavir/lamivudine
  • Plasma viral load (HIV-RNA) < 50 copies/ml at inclusion

For women of childbearing potential:

  • Negative pregnancy test
  • Willingness to use contraceptive (consistent with local regulations) during study period

Exclusion Criteria:

  • Pre-existing viral resistance mutations to lamivudine or to dolutegravir
  • Presence of hepatitis B antigen (HBsAg) or Hepatitis B virus DNA (HBV DNA)
  • Cancer within past 5 years
  • Diabetes, cardiovascular disease or other chronic illness considered stable as assessed by the treating physician

For women of childbearing potential:

  • Pregnancy
  • Breastfeeding

Information from the National Library of Medicine

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): NCT04904406


Contacts
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Contact: Karen BH Pedersen, MD +4521623027 karen.brorup.heje.pedersen@regionh.dk
Contact: Thomas L Benfield, MD, DMSc thomas.lars.benfield@regionh.dk

Locations
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Denmark
Aalborg University Hospital Not yet recruiting
Aalborg, Denmark, 9000
Contact: Henrik Nielsen, MD, DMSc         
Aarhus University Hospital Not yet recruiting
Aarhus, Denmark, 8200
Contact: Alex L Laursen, MD, DMSc         
Rigshospitalet Not yet recruiting
Copenhagen, Denmark, 2100
Contact: Jan Gerstoft, MD, DMSc         
Copenhagen University Hospital, Amager Hvidovre Recruiting
Hvidovre, Denmark, 2650
Contact: Thomas Benfield, MD    38622302    thomas.lars.benfield@regionh.dk   
Contact: Karen Brorup Pedersen, MD       karen.brorup.heje.pedersen@regionh.dk   
Odense University Hospital Not yet recruiting
Odense, Denmark, 5000
Contact: Isik S Johansen, MD, DMSc         
Sponsors and Collaborators
Thomas Benfield
Investigators
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Principal Investigator: Thomas Benfield, MD, DMSc Department of Infectious diseases, Hvidovre Hospital, Denmark
Publications:

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Responsible Party: Thomas Benfield, MD, professor, dr.med., Hvidovre University Hospital
ClinicalTrials.gov Identifier: NCT04904406    
Other Study ID Numbers: H-20011433
First Posted: May 27, 2021    Key Record Dates
Last Update Posted: May 27, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Thomas Benfield, Hvidovre University Hospital:
HIV
Weight changes
Antiretroviral Therapy
Cardiovascular disease
Antiretroviral therapy side effects
Antiretroviral two-drug regimen
HIV metabolism
HIV diabetes
Additional relevant MeSH terms:
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Infections
HIV Infections
Acquired Immunodeficiency Syndrome
Cardiovascular Diseases
Cardiomyopathies
Lipodystrophy
Body Weight
Body Weight Changes
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Heart Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Lamivudine
Abacavir
Dolutegravir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors