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

Switching From Lopinavir/Ritonavir Plus Tenofovir and Emtricitabine (or Lamivudine) to Darunavir (Prezista) and Raltegravir to Evaluate Renal Function

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Raltegravir, Darunavir/r

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

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Shinjuku, Tokyo, Japan, 1628655
      • National Center for Global Health and Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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; Other Names: NRTI sparing regimen
No Intervention: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR improvement comparison of two arms by ITT analysis	To investigate whether 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 study, or not.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological efficacy	Virological efficacy of the group on DRV/r+RAL	48 weeks up to 96 weeks
Renal function markers	Serum creatinine, eGFR, uine beta-2 microglobulin, tubular resorption rate of phosphate, urine albumin, N-acetyl-beta-glucosaminidase, serum cystatin C, urine protein and urine glucose	48 weeks up to 96 weeks
Lipids	Triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol	48 weeks up to 96 weeks
Adverse events	Adverse events of each arm, symptoms and rate	96 weeks
Blood plasma concentration of RAL and DRV	Blood plasma concentration level of raltegravir and darunavir among all consented and intervened cases at National Center for Global Health and Medicine	96 weeks
Discontinuation rate	Discontinuation rate of each arm, reason and timing	96 weeks

Collaborators and Investigators

• Sponsor: National Center for Global Health and Medicine, Japan
• Collaborators: Ministry of Health, Labour and Welfare, Japan
• Investigators: Principal Investigator: Shinichi Oka, MD PhD, National Center for Global Health and Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: February 10, 2011
• First Submitted That Met QC Criteria: February 10, 2011
• First Posted (Estimate): February 11, 2011

Study Record Updates

• Last Update Posted (Estimate): March 30, 2015
• Last Update Submitted That Met QC Criteria: March 27, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: HIV-1; AIDS; Clinical Trials, Randomized
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Darunavir
• Other Study ID Numbers: FWA00005823-SPARE2011; UMIN000005116 (Other Identifier: University Hospital Medical Information Network (UMIN))