Clinical trial NCT01294761: Comparing Continuing Tenofovir, Emtricitabine (or Lamivudine) Plus Lopinavir and Switching to Raltegravir Plus Darunavir
Official title: Switching From Lopinavir/Ritonavir Plus Tenofovir and Emtricitabine (or Lamivudine) to Darunavir (Prezista) and Raltegravir to Evaluate Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: HIV-1
AIDS
Clinical Trials, Randomized
Lead sponsor: National Center for Global Health and Medicine, Japan
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Health, Labour and Welfare, Japan
First posted: 2011-02-11
Enrollment: 59
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria: 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

Exclusion Criteria: cases applicable to any of the following will be excluded from this trial

* 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

Primary outcomes:
measure: eGFR improvement comparison of two arms by ITT analysis
timeFrame: 48 weeks
Secondary outcomes:
measure: Virological efficacy
timeFrame: 48 weeks up to 96 weeks
measure: Renal function markers
timeFrame: 48 weeks up to 96 weeks
measure: Lipids
timeFrame: 48 weeks up to 96 weeks
measure: Adverse events
timeFrame: 96 weeks
measure: Blood plasma concentration of RAL and DRV
timeFrame: 96 weeks
measure: Discontinuation rate
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Shinjuku
country: Japan
facility: National Center for Global Health and Medicine
state: Tokyo
Study officials:
affiliation: National Center for Global Health and Medicine
name: Shinichi Oka, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.