Europe-Africa Research Network for Evaluation of Second-line Therapy (EARNEST)

This study has been completed.
Sponsor:
Collaborator:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
Justine Boles, Medical Research Council
ClinicalTrials.gov Identifier:
NCT00988039
First received: September 30, 2009
Last updated: April 3, 2014
Last verified: April 2014

September 30, 2009
April 3, 2014
March 2010
January 2014   (final data collection date for 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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00988039 on ClinicalTrials.gov Archive Site
  • Good HIV disease control [ Time Frame: week 144 ] [ Designated as safety issue: No ]
  • Proportion with CD4 cell count >250 cells/mm3 [ Time Frame: week 96 and week 144 ] [ Designated as safety issue: No ]
  • Proportion with new or recurrent WHO stage 4 event [ Time Frame: week 96 and week 144 ] [ Designated as safety issue: Yes ]
  • Proportion of patients with plasma viral load <50 copies [ Time Frame: week 48, week 96 and week 144 ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: During trial ] [ Designated as safety issue: Yes ]
  • Quality of life change from randomisation [ Time Frame: During trial ] [ Designated as safety issue: No ]
  • Neurocognitive function change from randomisation [ Time Frame: during trial ] [ Designated as safety issue: No ]
  • Healthcare costs [ Time Frame: During trial ] [ Designated as safety issue: No ]
  • Proportion with serious non-AIDS events [ Time Frame: Week 96 and week 144 ] [ Designated as safety issue: No ]
  • Good HIV disease control [ Time Frame: week 144 ] [ Designated as safety issue: No ]
  • Proportion with CD4 cell count >250 cells/mm3 [ Time Frame: week 96 and week 144 ] [ Designated as safety issue: No ]
  • Proportion with new or recurrent WHO stage 4 event [ Time Frame: week 96 and week 144 ] [ Designated as safety issue: No ]
  • Proportion of patients with plasma viral load <50 copies [ Time Frame: week 48, week 96 and week 144 ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: During trial ] [ Designated as safety issue: No ]
  • Quality of life change from randomisation [ Time Frame: During trial ] [ Designated as safety issue: No ]
  • Neurocognitive function change from randomisation [ Time Frame: during trial ] [ Designated as safety issue: No ]
  • Healthcare costs [ Time Frame: During trial ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Europe-Africa Research Network for Evaluation of Second-line Therapy
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.

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
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Human Immunodeficiency Virus
  • HIV
  • Drug: Aluvia + 2NRTIs

    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.

  • Drug: Aluvia + raltegravir

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

    raltegravir (400mg) twice daily

  • Drug: Aluvia monotherapy

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

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

  • Active Comparator: bPI + 2NRTIs
    Intervention: Drug: Aluvia + 2NRTIs
  • Experimental: bPI + raltegravir
    Intervention: Drug: Aluvia + raltegravir
  • Experimental: bPI monotherapy
    Intervention: Drug: Aluvia monotherapy
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1277
January 2014
January 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
Both
12 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Kenya,   Uganda,   Malawi,   Zimbabwe,   Zambia
 
NCT00988039
U.1228.03.004.00021.01, IP_2007_33011_003, ISRCTN37737787
Yes
Justine Boles, Medical Research Council
Justine Boles
European and Developing Countries Clinical Trials Partnership (EDCTP)
Study Director: Nicholas Paton, MD FRCP MRC CTU
Medical Research Council
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP