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

Sponsor
Thomas Benfield (Other)
Overall Status
Recruiting
CT.gov ID
NCT04904406
Collaborator
(none)
95
Enrollment
5
Locations
2
Arms
25.3
Anticipated Duration (Months)
19
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
95 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A randomized controlled open-label superiority trialA 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 :
Oct 22, 2020
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

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 Names:
  • 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

    Outcome Measures

    Primary Outcome Measures

    1. Changes in body weight of ≥2 kg [48 weeks]

      Fasting body weight

    Secondary Outcome Measures

    1. Virological control [48 weeks]

      HIV-RNA <50 copies/ml

    2. Changes in self-rated health [48 weeks]

      12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best).

    3. Change in metabolism [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 [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) [48 weeks]

      Measured by ultrasound.

    6. Changes in Coronary artery calcium score (CACS) [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 [48 weeks]

      Changes in N-terminal pro-B-type natriuretic peptide (Pro-BNP)

    8. Changes in bloodpressure [48 weeks]

      Systolic and diastolic blood pressure (mmHg)

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

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

    10. Changes in liver stiffness [48 weeks]

      Measured by CT-scan and liver elastography

    11. Changes in liver fat infiltration [48 weeks]

      Measured by CT-scan and liver elastography

    12. Changes in fat distribution in trunk, limb and extremities [48 weeks]

      Measured by dual energy xray absorptiometry (DEXA)

    13. Changes in inflammation [48 weeks]

      High-sensitive C-reactive protein

    14. Changes in interleukins [48 weeks]

      Interleukin 1- and interleukin 6

    15. Changes in endothelial function [48 weeks]

      Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1

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

      soluble P-selectin

    17. Changes in soluble glycoprotein VI [48 weeks]

      soluble glycoprotein VI

    18. Changes in d-dimer [48 weeks]

      D-dimer

    19. Changes in coagulation [48 weeks]

      Factor 2, 7 and 10 (extrinsic pathway)

    20. Changes in fibrinogen [48 weeks]

      Fibrinogen

    21. Changes in blood Hemoglobin [48 weeks]

      Hemoglobin

    22. Changes in blood platelets [48 weeks]

      Platelets

    23. Changes in plasma creatinine [48 weeks]

      Creatinine

    24. Changes in plasma urea [48 weeks]

      Urea

    25. Changes in plasma sodium [48 weeks]

      Sodium

    26. Changes in plasma potassium [48 weeks]

      Potassium

    27. Changes in plasma bilirubin [48 weeks]

      Bilirubin

    28. Changes in plasma alanine [48 weeks]

      Alanine

    29. Changes in plasma aminotransferase [48 weeks]

      Aminotransferase

    30. Cardiovascular risk [48 weeks]

      Framingham risk score: Estimated 10 years risk of cardiovascular disease (percent)

    31. Cardiac biomarkers [48 weeks]

      Changes in Troponin T (TnT)

    Other Outcome Measures

    1. Cardiac MRI substudy primary outcome (composite) ECV [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 [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 [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 [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) [48 weeks]

      Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Ejection fraction (EF)

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

      Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Perfusion

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

      Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Edema/inflammation

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

      Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Fibrosis

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

      Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Lipid-water profile Measured by MR spectroscopy

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Aalborg University Hospital Aalborg Denmark 9000
    2 Aarhus University Hospital Aarhus Denmark 8200
    3 Rigshospitalet Copenhagen Denmark 2100
    4 Copenhagen University Hospital, Amager Hvidovre Hvidovre Denmark 2650
    5 Odense University Hospital Odense Denmark 5000

    Sponsors and Collaborators

    • Thomas Benfield

    Investigators

    • Principal Investigator: Thomas Benfield, MD, DMSc, Department of Infectious diseases, Hvidovre Hospital, Denmark

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    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
    Last Update Posted:
    May 27, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Thomas Benfield, MD, professor, dr.med., 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:
    Infections
    HIV Infections
    Acquired Immunodeficiency Syndrome
    Cardiovascular Diseases
    Cardiomyopathies
    Lipodystrophy
    Body Weight
    Body Weight Changes
    Lamivudine
    Abacavir
    Dolutegravir

    Study Results

    No Results Posted as of May 27, 2021