Comparing Continuing Tenofovir, Emtricitabine (or Lamivudine) Plus Lopinavir and Switching to Raltegravir Plus Darunavir

NCT ID: NCT01294761

Last Updated: 2015-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2013-12-31

Brief Summary

The main objective of this clinical trial in randomizing HIV infected patients under good HIV control with tenofovir (TDF), emtricitabine (or lamivudine) plus lopinavir/ritonavir (LPV/r) into switching the regimen to raltegravir (RAL) with darunavir/ritonavir (DRV/r) or continuing the ongoing regimen to compare these two groups' estimated glomerular filtration rate (eGFR) is to investigate whether anti-HIV treatment that does not contain TDF or other reverse-transcriptase inhibitors (NTRI sparing regimen) can be protective of patients' renal functions and has the same virological efficacy in comparison with a standard treatment with TDF, or not.

Detailed Description

Eligibility criteria are HIV infected outpatients or inpatients that are:

without history virological failure including protease inhibitors or raltegravir (disregarding whether the patient had a history of drug resistance or drug holiday, or not) taking LPV/r+TVD (or TDF+lamivudine) for longer than 15 weeks before the enrollment with HIV viral load less than 50 copies/ml for 15 weeks, including those with blips (one time episode of detectable level HIV viraemia which are proceeded and followed by undetectable viraemia).

20 years old or older Japanese willing to participate in the trial and able to agree to the informed consent. Main outcome measures are to investigate if the estimated glomerular filtration rate (eGFR) of the intervened group with RAL+DRV/r improves by 10% or more by intention to treat (ITT) analysis at the time of 48 weeks after the start of the trial.

Other outcome measures are:

virological efficacy of the group on DRV/r+RAL (after 48 weeks and up to 96 weeks) comparison of other renal function markers between the two arms: serum creatinine, urine beta-2 microglobulin, tubular resorption rate of phosphate, urine albumin, N-acetyl-beta-glucosaminidase, serum cystatin C, urine protein and urine glucose (after 48 weeks and up to 96 weeks) comparison of lipid markers between the two arms: triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol (after 48 weeks and up to 96 weeks) discontinuation rate of each arm, reason and timing of the discontinuation or the treatment change up to 96 weeks adverse events of each arm, symptoms and rate up to 96 weeks blood plasma concentration level of RAL and DRV of all consented intervened cases at National Center for Global Health and Medicine

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Raltegravir, Darunavir/r

An arm to change the regimen from: Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD

to: Prezista naive 2 tabs PC QD, Norvir soft-capsule 1 cap PC QD and Isentress 1 tab BID or Prezista 2 tabs PC BID and Norvir soft-capsule 1 cap PC BID, and Isentress 1 tab BID

Group Type: EXPERIMENTAL

Raltegravir, Darunavir/r

Intervention Type: DRUG

An arm to change the regimen to: raltegravir and darunavir/ritonavir

Prezista naive 2 tabs PC QD, Norvir soft-capsule 1 cap PC QD and Isentress 1 tab BID or Prezista 2 tabs PC BID and Norvir soft-capsule 1 cap PC BID, and Isentress 1 tab BID

from: Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD

Tenofovir, Emtricitabine, Lopinavir/r

An arm continuing on the same regimen before the randomization as Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Raltegravir, Darunavir/r

An arm to change the regimen to: raltegravir and darunavir/ritonavir

Prezista naive 2 tabs PC QD, Norvir soft-capsule 1 cap PC QD and Isentress 1 tab BID or Prezista 2 tabs PC BID and Norvir soft-capsule 1 cap PC BID, and Isentress 1 tab BID

from: Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD

Intervention Type: DRUG

Other Intervention Names

NRTI sparing regimen

Eligibility Criteria

Inclusion Criteria

• without history virological failure including protease inhibitors or raltegravir (disregarding whether the patient had a history of drug resistance or drug holiday, or not)
• taking LPV/r+TVD (or TDF+lamivudine) for longer than 15 weeks before the enrollment
• with HIV viral load less than 50 copies/ml for 15 weeks, including those with blips (one time episode of detectable level HIV viraemia which are proceeded and followed by undetectable viraemia)
• 20 years old or older
• Japanese
• willing to participate in the trial and able to agree to the informed consent

Exclusion Criteria

• HBs antigen positive within 15 weeks to the enrollment (cases confirmed as HBs antibody positive can be enrolled without HBs antigen testing)
• malabsorption or gastrointestinal symptoms that affect absorption of the drugs, or dysphagia cases
• clinical data within 15 weeks before the start of the trial and of the closest date to the enrollment that are GPT 2.5 times the highest of the normal range (grade 2) or eGFR less than 60ml/min (Cockcroft-Gault formula)
• cases with opportunistic infections requiring treatment (primary and secondary preventive prophylaxis can be administrated during the study)
• cases during pregnancy or nursing period, or with a possibility for pregnancy
• using drugs that are prohibited to combine for drug interaction with the drugs of this trial
• other cases that are decided by the patient's physician as not suitable for the trial

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Labour and Welfare, Japan

OTHER_GOV

Sponsor Role: collaborator

National Center for Global Health and Medicine, Japan

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shinichi Oka, MD PhD

Role: PRINCIPAL_INVESTIGATOR

National Center for Global Health and Medicine

Locations

National Center for Global Health and Medicine

Shinjuku, Tokyo, Japan

Countries

Japan

References

Nishijima T, Gatanaga H, Shimbo T, Komatsu H, Endo T, Horiba M, Koga M, Naito T, Itoda I, Tei M, Fujii T, Takada K, Yamamoto M, Miyakawa T, Tanabe Y, Mitsuya H, Oka S; SPARE study team. Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus Darunavir/r in patients with suppressed viral load did not result in improvement of renal function but could sustain viral suppression: a randomized multicenter trial. PLoS One. 2013 Aug 8;8(8):e73639. doi: 10.1371/journal.pone.0073639. eCollection 2013.

Reference Type: RESULT

PMID: 23951362 (View on PubMed)

Other Identifiers

UMIN000005116

Identifier Type: OTHER

Identifier Source: secondary_id

FWA00005823-SPARE2011

Identifier Type: -

Identifier Source: org_study_id