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HivPhase 4AVERTASNCT04904406

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

A Phase 4 study testing Dolutegravir / Lamivudine Oral Tablet in people with Hiv and HIV Infections, run by Thomas Benfield at 2 sites in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hiv, HIV Infections, HIV Cardiomyopathy
What is being tested?
Dolutegravir / Lamivudine Oral Tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
81 participants
Where
2 sitesDenmark
Study dates
22 Oct 2020to 1 Dec 2023
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

Denmark2 sites

  • Copenhagen University Hospital - Rigshospitalet

    Copenhagen, 2100

  • Copenhagen University Hospital, Amager Hvidovre

    Hvidovre, 2650

Other trials in Denmark

About this study

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

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.

Read the 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.

Being tested
Dolutegravir / Lamivudine Oral Tablet
Keywords
HIV, Weight changes, Antiretroviral Therapy, Cardiovascular disease, Antiretroviral therapy side effects, Antiretroviral two-drug regimen, HIV metabolism, HIV diabetes
Medical subject headings
Acquired Immunodeficiency Syndrome, HIV Infections, Body Weight Changes, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dolutegravir / Lamivudine Oral TabletDrug

    Also called Dolutegravir/abacavir/lamivudine

    Discontinuing abacavir by switching from three-drug regimen with dolutegravir/abacavir/lamivudine to two-drug regimen with dolutegravir/lamivudine

Study groups in NCT04904406
Study groupRoleWhat they receive
dolutegravir/lamivudineExperimental50 mg dolutegravir and 300 mg lamivudine (co-formulated) once daily for 48 weeks
Receives: Drug: Dolutegravir / Lamivudine Oral Tablet
dolutegravir/abacavir/lamivudineNo intervention50 mg dolutegravir, 600 mg abacavir and 300 mg lamivudine (co-formulated) once daily for 48 weeks

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in body weight of ≥2 kg

    Fasting body weight

    Measured: 48 weeks

Secondary outcomes (31)

  1. Virological control

    HIV-RNA <50 copies/ml

    Measured: 48 weeks

  2. Changes in self-rated health

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

    Measured: 48 weeks

  3. Change in metabolism

    Impaired insulin resistance and/or β-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

    Measured: 48 weeks

  4. Changes in cardiac risk

    D:A:D CVD risk score: Five and ten years predicted cardio vascular disease risk (percent)

    Measured: 48 weeks

  5. Changes in carotid artery intima-media thickness (cIMT)

    Measured by ultrasound.

    Measured: 48 weeks

  6. Changes in Coronary artery calcium score (CACS)

    Measures by CT-scan. Scores from 0 and with no upper limit. The higher score, the worse calcification/plaque level and higher CVD risk.

    Measured: 48 weeks

  7. Changes in cardiac blood markers

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

    Measured: 48 weeks

  8. Changes in bloodpressure

    Systolic and diastolic blood pressure (mmHg)

    Measured: 48 weeks

  9. Changes in fat distribution VAT/SAT

    Measured by CT-scan

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

    Measured: 48 weeks

  10. Changes in liver stiffness

    Measured by CT-scan and liver elastography

    Measured: 48 weeks

  11. Changes in liver fat infiltration

    Measured by CT-scan and liver elastography

    Measured: 48 weeks

  12. Changes in fat distribution in trunk, limb and extremities

    Measured by dual energy xray absorptiometry (DEXA)

    Measured: 48 weeks

  13. Changes in inflammation

    High-sensitive C-reactive protein

    Measured: 48 weeks

  14. Changes in interleukins

    Interleukin 1- and interleukin 6

    Measured: 48 weeks

  15. Changes in endothelial function

    Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1

    Measured: 48 weeks

  16. Changes in soluble P-selectin

    soluble P-selectin

    Measured: 48 weeks

  17. Changes in soluble glycoprotein VI

    soluble glycoprotein VI

    Measured: 48 weeks

  18. Changes in d-dimer

    D-dimer

    Measured: 48 weeks

  19. Changes in coagulation

    Factor 2, 7 and 10 (extrinsic pathway)

    Measured: 48 weeks

  20. Changes in fibrinogen

    Fibrinogen

    Measured: 48 weeks

  21. Changes in blood Hemoglobin

    Hemoglobin

    Measured: 48 weeks

  22. Changes in blood platelets

    Platelets

    Measured: 48 weeks

  23. Changes in plasma creatinine

    Creatinine

    Measured: 48 weeks

  24. Changes in plasma urea

    Urea

    Measured: 48 weeks

  25. Changes in plasma sodium

    Sodium

    Measured: 48 weeks

  26. Changes in plasma potassium

    Potassium

    Measured: 48 weeks

  27. Changes in plasma bilirubin

    Bilirubin

    Measured: 48 weeks

  28. Changes in plasma alanine

    Alanine

    Measured: 48 weeks

  29. Changes in plasma aminotransferase

    Aminotransferase

    Measured: 48 weeks

  30. Cardiovascular risk

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

    Measured: 48 weeks

  31. Cardiac biomarkers

    Changes in Troponin T (TnT)

    Measured: 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2021
  2. Study start22 Oct 2020
  3. Primary completion1 Dec 2023
  4. Study completion1 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
A randomized controlled open-label superiority trial
Masking
None (open label)
Enrolment
81 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04904406
Sponsor's protocol ID
H-20011433
Acronym
AVERTAS
Status last verified
May 2024
First submitted
9 Oct 2020
Last updated
29 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Belloso WH, Orellana LC, Grinsztejn B, Madero JS, La Rosa A, Veloso VG, Sanchez J, Ismerio Moreira R, Crabtree-Ramirez B, Garcia Messina O, Lasala MB, Peinado J, Losso MH. Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites. HIV Med. 2010 Oct 1;11(9):554-64. doi: 10.1111/j.1468-1293.2010.00824.x. Epub 2010 Mar 21.

    PubMed 20345879

  • Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte Ad, Phillips AN, Sabin CA, Lundgren JD; D:A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014 Jul 19;384(9939):241-8. doi: 10.1016/S0140-6736(14)60604-8.

    PubMed 25042234

  • Freiberg MS, Chang CC, Kuller LH, Skanderson M, Lowy E, Kraemer KL, Butt AA, Bidwell Goetz M, Leaf D, Oursler KA, Rimland D, Rodriguez Barradas M, Brown S, Gibert C, McGinnis K, Crothers K, Sico J, Crane H, Warner A, Gottlieb S, Gottdiener J, Tracy RP, Budoff M, Watson C, Armah KA, Doebler D, Bryant K, Justice AC. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013 Apr 22;173(8):614-22. doi: 10.1001/jamainternmed.2013.3728.

    PubMed 23459863

  • Sabin CA, Reiss P, Ryom L, Phillips AN, Weber R, Law M, Fontas E, Mocroft A, de Wit S, Smith C, Dabis F, d'Arminio Monforte A, El-Sadr W, Lundgren JD; D:A:D Study Group. Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration. BMC Med. 2016 Mar 31;14:61. doi: 10.1186/s12916-016-0588-4.

    PubMed 27036962

  • Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, De Wit S, Law M, Monforte AD, Friis-Moller N, Kirk O, Fontas E, Weller I, Phillips A, Lundgren J. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis. 2010 Feb 1;201(3):318-30. doi: 10.1086/649897.

    PubMed 20039804

  • D:A:D Study Group; Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, De Wit S, Law M, D'Arminio Monforte A, Friis-Moller N, Kirk O, Pradier C, Weller I, Phillips AN, Lundgren JD. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008 Apr 26;371(9622):1417-26. doi: 10.1016/S0140-6736(08)60423-7. Epub 2008 Apr 2.

    PubMed 18387667

  • Venter WDF, Moorhouse M, Sokhela S, Fairlie L, Mashabane N, Masenya M, Serenata C, Akpomiemie G, Qavi A, Chandiwana N, Norris S, Chersich M, Clayden P, Abrams E, Arulappan N, Vos A, McCann K, Simmons B, Hill A. Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV. N Engl J Med. 2019 Aug 29;381(9):803-815. doi: 10.1056/NEJMoa1902824. Epub 2019 Jul 24.

    PubMed 31339677

  • Lake JE, Wu K, Bares SH, Debroy P, Godfrey C, Koethe JR, McComsey GA, Palella FJ, Tassiopoulos K, Erlandson KM. Risk Factors for Weight Gain Following Switch to Integrase Inhibitor-Based Antiretroviral Therapy. Clin Infect Dis. 2020 Dec 3;71(9):e471-e477. doi: 10.1093/cid/ciaa177.

    PubMed 32099991

  • Hill A, Waters L, Pozniak A. Are new antiretroviral treatments increasing the risks of clinical obesity? J Virus Erad. 2019 Jan 1;5(1):41-43. doi: 10.1016/S2055-6640(20)30277-6.

    PubMed 30800425

  • Sax PE, Erlandson KM, Lake JE, Mccomsey GA, Orkin C, Esser S, Brown TT, Rockstroh JK, Wei X, Carter CC, Zhong L, Brainard DM, Melbourne K, Das M, Stellbrink HJ, Post FA, Waters L, Koethe JR. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. Clin Infect Dis. 2020 Sep 12;71(6):1379-1389. doi: 10.1093/cid/ciz999.

    PubMed 31606734

  • Choi AI, Vittinghoff E, Deeks SG, Weekley CC, Li Y, Shlipak MG. Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons. AIDS. 2011 Jun 19;25(10):1289-98. doi: 10.1097/QAD.0b013e328347fa16.

    PubMed 21516027

  • Desai M, Joyce V, Bendavid E, Olshen RA, Hlatky M, Chow A, Holodniy M, Barnett P, Owens DK. Risk of cardiovascular events associated with current exposure to HIV antiretroviral therapies in a US veteran population. Clin Infect Dis. 2015 Aug 1;61(3):445-52. doi: 10.1093/cid/civ316. Epub 2015 Apr 22.

    PubMed 25908684

  • O'Halloran JA, Dunne E, Tinago W, Denieffe S, Kenny D, Mallon PWG. Switching from abacavir to tenofovir disoproxil fumarate is associated with rises in soluble glycoprotein VI, suggesting changes in platelet-collagen interactions. AIDS. 2018 Apr 24;32(7):861-866. doi: 10.1097/QAD.0000000000001783.

    PubMed 29438200

  • Freiberg MS, Chang CH, Skanderson M, Patterson OV, DuVall SL, Brandt CA, So-Armah KA, Vasan RS, Oursler KA, Gottdiener J, Gottlieb S, Leaf D, Rodriguez-Barradas M, Tracy RP, Gibert CL, Rimland D, Bedimo RJ, Brown ST, Goetz MB, Warner A, Crothers K, Tindle HA, Alcorn C, Bachmann JM, Justice AC, Butt AA. Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study. JAMA Cardiol. 2017 May 1;2(5):536-546. doi: 10.1001/jamacardio.2017.0264.

    PubMed 28384660

  • Thiara DK, Liu CY, Raman F, Mangat S, Purdy JB, Duarte HA, Schmidt N, Hur J, Sibley CT, Bluemke DA, Hadigan C. Abnormal Myocardial Function Is Related to Myocardial Steatosis and Diffuse Myocardial Fibrosis in HIV-Infected Adults. J Infect Dis. 2015 Nov 15;212(10):1544-51. doi: 10.1093/infdis/jiv274. Epub 2015 May 11.

    PubMed 25964507

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dolutegravir / Lamivudine Oral Tablet in people with Hiv and HIV Infections, run by Thomas Benfield at 2 sites in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in body weight of ≥2 kg (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04904406, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2024.

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