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Human Immunodeficiency VirusPhase 3EARNESTNCT00988039

Europe-Africa Research Network for Evaluation of Second-line Therapy

A Phase 3 study testing Aluvia + 2NRTIs, Aluvia + raltegravir and Aluvia monotherapy in people with Human Immunodeficiency Virus and HIV, run by Justine Boles at 14 sites in 5 countries.

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

The trial aim is to ascertain what, if anything, needs to be combined with a boosted protease inhibitor (bPI) backbone in second-line therapy in order to maximize the chance of a good clinical outcome following WHO-defined failure on a first-line nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI-containing… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Human Immunodeficiency Virus, HIV
What is being tested?
Aluvia + 2NRTIs, Aluvia + raltegravir and Aluvia monotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,277 participants
Where
14 sitesin 5 countries
Study dates
Mar 2010to Jan 2014
Phase
Phase 3
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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Previously documented HIV infection on at least one standard antibody-based test
  • Age 12 years and above
  • Taking 2NRTI + NNRTI-based regimen continuously for at least 12 months
  • Naive to protease inhibitor therapy
  • Good adherence to ART in the 12 weeks prior to screening defined as missing medication on no more than 3 days in the prior month
  • Clinically stable and receiving treatment for any known opportunistic infections
Show all 9Show fewer
  • HIV treatment failure defined by one or more of clinical, immunological or virological criteria defined in the protocol, including VL and CD4 at screening visit
  • Willing and able to give informed consent
  • Able to attend for regular study follow up visits

Who cannot join

  • Any major clinical contra-indications to the use of bPI, the NRTIs that are available to be selected for a second-line regimen or raltegravir
  • Known Hepatitis B carrier (Hepatitis B surface antigen positive if tested)
  • Requires concomitant medication with known major interactions with study drugs for which drug substitutions or dose alterations are not available or acceptable
  • Women who are currently pregnant or breastfeeding
  • Current participation in another clinical trial involving a treatment intervention (may be permitted in some circumstances, but must be discussed with MRC CTU)
  • Life expectancy of less than one month in the opinion of the treating physician

Trial locations and contacts

14 sites in 5 countries.

14 sites in 5 countries

Uganda9 sites

  • Joint Clinical Research Centre

    Fort Portal

  • JCRC

    Gulu

  • JCRC

    Kabale

  • JCRC

    Kakira

  • Infectious Diseases Institute

    Kampala

  • Joint Clinical Research Centre

    Kampala

  • San Raphael of St Francis Hospital Nsambya

    Kampala

  • Joint Clinical Research Centre

    Mbale

  • Joint Clinical Research Centre

    Mbarara

Other trials in Uganda

Malawi2 sites

  • University of Malawi

    Blantyre

  • Mzuzu Central Hospital

    Mzuzu

Other trials in Malawi

Kenya1 site

  • AMPATH Centre at Moi Teaching Referral Hospital

    Eldoret

Other trials in Kenya

Zambia1 site

  • University Teaching Hospital

    Lusaka

Other trials in Zambia

Zimbabwe1 site

  • University of Zimbabwe Clinical Research Centre

    Harare

Other trials in Zimbabwe

About this study

Official title: A Randomised Controlled Trial to Evaluate Options for Second-line Therapy in Patients Failing a First-line 2NRTI + NNRTI Regimen in Africa

The trial aim is to ascertain what, if anything, needs to be combined with a boosted protease inhibitor (bPI) backbone in second-line therapy in order to maximize the chance of a good clinical outcome following WHO-defined failure on a first-line nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI-containing regimen with probable extensive NRTI and NNRTI resistance mutations.

Read the detailed description

The standard of care for second-line HIV therapy in patients who have failed a first-line NNRTI-based regimen is to combine a boosted protease inhibitor (bPI) with two (new) NRTIs. However, patients failing first-line therapy in roll-out programmes often have extensive NRTI resistance mutations that may compromise the efficacy of the NRTI drugs used in second-line therapy and it is likely that the virological potency of the second-line regimen is mostly due to the bPI. It is possible that the contribution of the NRTI drugs to efficacy may be outweighed by additional toxicity and cost. It is also possible that replacing the NRTI drugs with a new class of drug (integrase inhibitors) will improve outcome from second-line therapy, although if the boosted protease inhibitor alone is providing close to optimal response, incremental gains from adding a new class may be small.

The principal aims are to determine whether, in patients failing a first-line NRTI and NNRTI-containing regimen:

  • The use of bPI plus raltegravir (an integrase inhibitor) is superior to standard of care (bPI plus 2 new NRTIs) in achieving good HIV disease control at 96 weeks after randomisation
  • The use of bPI monotherapy, preceded by a 12-week induction period in combination with raltegravir, is non-inferior to standard of care in achieving good HIV disease control at 96 weeks after randomisation
Being tested
Aluvia + 2NRTIs, Aluvia + raltegravir, Aluvia monotherapy
Keywords
Human Immunodeficiency virus, second line therapy, raltegravir, aluvia, monotherapy, integrase inhibitor, protease inhibitor, Randomized Controlled Trial
Medical subject headings
Acquired Immunodeficiency Syndrome

What participants receive

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

  • Aluvia + 2NRTIsDrug

    Aluvia (lopinavir/ritonavir 400mg/100mg), twice daily

    The choice of NRTIs will be at the discretion of the managing clinician and based on the local standard of care and drug availability, taking into account patient's previous drug exposure and side effects on first-line therapy.

  • Aluvia + raltegravirDrug

    Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily

    raltegravir (400mg) twice daily

  • Aluvia monotherapyDrug

    Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily

    raltegravir (400mg) twice daily for the first 12 weeks only

Study groups in NCT00988039
Study groupRoleWhat they receive
bPI + 2NRTIsActive comparatorNot described
Receives: Drug: Aluvia + 2NRTIs
bPI + raltegravirExperimentalNot described
Receives: Drug: Aluvia + raltegravir
bPI monotherapyExperimentalNot described
Receives: Drug: Aluvia monotherapy

What is being measured

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

  1. Good HIV disease control defined as a composite endpoint consisting of all of: - No new WHO stage 4 events - CD4 count >250 cells/mm3 - viral load <10,000 copies/ml or >10,000 copies/ml with no PI resistance mutations

    Measured: week 96

Secondary outcomes (9)

  1. Good HIV disease control

    Measured: week 144

  2. Proportion with CD4 cell count >250 cells/mm3

    Measured: week 96 and week 144

  3. Proportion with new or recurrent WHO stage 4 event

    Measured: week 96 and week 144

  4. Proportion of patients with plasma viral load <50 copies

    Measured: week 48, week 96 and week 144

  5. Adverse events

    Measured: During trial

  6. Quality of life change from randomisation

    Measured: During trial

  7. Neurocognitive function change from randomisation

    Measured: during trial

  8. Healthcare costs

    Measured: During trial

  9. Proportion with serious non-AIDS events

    Measured: Week 96 and week 144

Timeline

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

  1. First posted1 Oct 2009 (estimated)
  2. Study startMar 2010
  3. Primary completionJan 2014
  4. Study completionJan 2014

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,277 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00988039
Sponsor's protocol ID
U.1228.03.004.00021.01
Other IDs
IP_2007_33011_003, ISRCTN37737787
Acronym
EARNEST
Status last verified
Apr 2014
First submitted
30 Sep 2009
Last updated
4 Apr 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Shi Y, Thompson J, Walker AS, Paton NI, Cheung YB; EARNEST Trial Team. Mapping the medical outcomes study HIV health survey (MOS-HIV) to the EuroQoL 5 Dimension (EQ-5D-3 L) utility index. Health Qual Life Outcomes. 2019 May 10;17(1):83. doi: 10.1186/s12955-019-1135-8.

    PubMed 31077251

  • Thompson JA, Kityo C, Dunn D, Hoppe A, Ndashimye E, Hakim J, Kambugu A, van Oosterhout JJ, Arribas J, Mugyenyi P, Walker AS, Paton NI; Europe-Africa Research Network for Evaluation of Second-line Therapy (EARNEST) Trial Team. Evolution of Protease Inhibitor Resistance in Human Immunodeficiency Virus Type 1 Infected Patients Failing Protease Inhibitor Monotherapy as Second-line Therapy in Low-income Countries: An Observational Analysis Within the EARNEST Randomized Trial. Clin Infect Dis. 2019 Mar 19;68(7):1184-1192. doi: 10.1093/cid/ciy589.

    PubMed 30060027

  • Paton NI, Kityo C, Thompson J, Nankya I, Bagenda L, Hoppe A, Hakim J, Kambugu A, van Oosterhout JJ, Kiconco M, Bertagnolio S, Easterbrook PJ, Mugyenyi P, Walker AS; Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST) Trial Team. Nucleoside reverse-transcriptase inhibitor cross-resistance and outcomes from second-line antiretroviral therapy in the public health approach: an observational analysis within the randomised, open-label, EARNEST trial. Lancet HIV. 2017 Aug;4(8):e341-e348. doi: 10.1016/S2352-3018(17)30065-6. Epub 2017 May 8.

    PubMed 28495562

  • Paton NI, Kityo C, Hoppe A, Reid A, Kambugu A, Lugemwa A, van Oosterhout JJ, Kiconco M, Siika A, Mwebaze R, Abwola M, Abongomera G, Mweemba A, Alima H, Atwongyeire D, Nyirenda R, Boles J, Thompson J, Tumukunde D, Chidziva E, Mambule I, Arribas JR, Easterbrook PJ, Hakim J, Walker AS, Mugyenyi P; EARNEST Trial Team. Assessment of second-line antiretroviral regimens for HIV therapy in Africa. N Engl J Med. 2014 Jul 17;371(3):234-47. doi: 10.1056/NEJMoa1311274.

    PubMed 25014688

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Aluvia + 2NRTIs, Aluvia + raltegravir and Aluvia monotherapy in people with Human Immunodeficiency Virus and HIV, run by Justine Boles at 14 sites in 5 countries.

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 9 inclusion and 6 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 4 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Uganda, Malawi, Kenya, Zambia, Zimbabwe. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Good HIV disease control defined as a composite endpoint consisting of all of: - No new WHO stage 4 events - CD4 count >250 cells/mm3 - viral load <10,000 copies/ml or >10,000 copies/ml with no PI resistance mutations (time frame: week 96). 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 NCT00988039, which also lists 4 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 4 Apr 2014.

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