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

HIV Clinical Trial

— EARNEST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00988039
• Other study ID #: U.1228.03.004.00021.01
• Secondary ID: IP_2007_33011_00
• Status: Completed
• Phase: Phase 3
• First received: September 30, 2009
• Last updated: April 3, 2014
• Start date: March 2010
• Est. completion date: January 2014

Study information

• Verified date: April 2014
• Source: Medical Research Council
• Contact: n/a
• Is FDA regulated: No
• Health authority: Uganda: National Council for Science and TechnologyUganda: National Drug AuthorityZimbabwe: Medicines Control Authority of ZimbabweMalawi: Pharmacy, Medicines and Poisons BoardZambia: Zambia Pharmaceutical Regulatory AuthorityKenya: Pharmacy and Poisons Board
• Study type: Interventional

Clinical 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 regimen with probable extensive NRTI and NNRTI resistance mutations.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1277
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes

Intervention

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.
• Aluvia + raltegravir
Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily raltegravir (400mg) twice daily
• Aluvia monotherapy
Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily raltegravir (400mg) twice daily for the first 12 weeks only

Locations

Country	Name	City	State
Kenya	AMPATH Centre at Moi Teaching Referral Hospital	Eldoret
Malawi	University of Malawi	Blantyre
Malawi	Mzuzu Central Hospital	Mzuzu
Uganda	Joint Clinical Research Centre	Fort Portal
Uganda	JCRC	Gulu
Uganda	JCRC	Kabale
Uganda	JCRC	Kakira
Uganda	Infectious Diseases Institute	Kampala
Uganda	Joint Clinical Research Centre	Kampala
Uganda	San Raphael of St Francis Hospital Nsambya	Kampala
Uganda	Joint Clinical Research Centre	Mbale
Uganda	Joint Clinical Research Centre	Mbarara
Zambia	University Teaching Hospital	Lusaka
Zimbabwe	University of Zimbabwe Clinical Research Centre	Harare

Sponsors (2)

Lead Sponsor	Collaborator
Justine Boles	European and Developing Countries Clinical Trials Partnership (EDCTP)

Countries where clinical trial is conducted

Kenya,  Malawi,  Uganda,  Zambia,  Zimbabwe, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		week 96	No
Secondary	Good HIV disease control		week 144	No
Secondary	Proportion with CD4 cell count >250 cells/mm3		week 96 and week 144	No
Secondary	Proportion with new or recurrent WHO stage 4 event		week 96 and week 144	Yes
Secondary	Proportion of patients with plasma viral load <50 copies		week 48, week 96 and week 144	No
Secondary	Adverse events		During trial	Yes
Secondary	Quality of life change from randomisation		During trial	No
Secondary	Neurocognitive function change from randomisation		during trial	No
Secondary	Healthcare costs		During trial	No
Secondary	Proportion with serious non-AIDS events		Week 96 and week 144	No

External Links

•   EARNEST trial website