Europe-Africa Research Network for Evaluation of Second-line Therapy (EARNEST)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Human Immunodeficiency Virus HIV |
Drug: Aluvia + 2NRTIs Drug: Aluvia + raltegravir Drug: Aluvia monotherapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomised Controlled Trial to Evaluate Options for Second-line Therapy in Patients Failing a First-line 2NRTI + NNRTI Regimen in Africa |
- 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 ]
- 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 ]
| Enrollment: | 1277 |
| Study Start Date: | March 2010 |
| Estimated Study Completion Date: | January 2014 |
| Estimated Primary Completion Date: | January 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: bPI + 2NRTIs |
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. |
| Experimental: bPI + raltegravir |
Drug: Aluvia + raltegravir
Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily raltegravir (400mg) twice daily |
| Experimental: bPI monotherapy |
Drug: Aluvia monotherapy
Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily raltegravir (400mg) twice daily for the first 12 weeks only |
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
Eligibility| Ages Eligible for Study: | 12 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Kenya | |
| AMPATH Centre at Moi Teaching Referral Hospital | |
| Eldoret, Kenya | |
| Malawi | |
| University of Malawi | |
| Blantyre, Malawi | |
| Mzuzu Central Hospital | |
| Mzuzu, Malawi | |
| Uganda | |
| Joint Clinical Research Centre | |
| Fort Portal, Uganda | |
| JCRC | |
| Gulu, Uganda | |
| JCRC | |
| Kabale, Uganda | |
| JCRC | |
| Kakira, Uganda | |
| Joint Clinical Research Centre | |
| Kampala, Uganda | |
| Infectious Diseases Institute | |
| Kampala, Uganda | |
| San Raphael of St Francis Hospital Nsambya | |
| Kampala, Uganda | |
| Joint Clinical Research Centre | |
| Mbale, Uganda | |
| Joint Clinical Research Centre | |
| Mbarara, Uganda | |
| Zambia | |
| University Teaching Hospital | |
| Lusaka, Zambia | |
| Zimbabwe | |
| University of Zimbabwe Clinical Research Centre | |
| Harare, Zimbabwe | |
| Study Director: | Nicholas Paton, MD FRCP | MRC CTU |
More Information
Additional Information:
No publications provided
| Responsible Party: | Justine Boles, Professor Nicholas Paton, Medical Research Council |
| ClinicalTrials.gov Identifier: | NCT00988039 History of Changes |
| Other Study ID Numbers: | U.1228.03.004.00021.01, IP_2007_33011_003, ISRCTN37737787 |
| Study First Received: | September 30, 2009 |
| Last Updated: | July 30, 2012 |
| Health Authority: | Uganda: National Council for Science and Technology Uganda: National Drug Authority Zimbabwe: Medicines Control Authority of Zimbabwe Malawi: Pharmacy, Medicines and Poisons Board Zambia: Zambia Pharmaceutical Regulatory Authority Kenya: Pharmacy and Poisons Board |
Keywords provided by Medical Research Council:
|
Human Immunodeficiency virus second line therapy raltegravir aluvia |
monotherapy integrase inhibitor protease inhibitor Randomized Controlled Trial |
Additional relevant MeSH terms:
|
Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Immune System Diseases Integrase Inhibitors |
Lopinavir Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions HIV Protease Inhibitors Protease Inhibitors Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013