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

HIV Infections Clinical Trial

— SPARE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01294761
• Other study ID #: FWA00005823-SPARE2011
• Secondary ID: UMIN000005116
• Status: Completed
• Phase: N/A
• First received: February 10, 2011
• Last updated: March 27, 2015
• Start date: February 2011
• Est. completion date: December 2013

Study information

• Verified date: March 2015
• Source: National Center for Global Health and Medicine, Japan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: December 2013
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

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

Locations

Country	Name	City	State
Japan	National Center for Global Health and Medicine	Shinjuku	Tokyo

Sponsors (2)

Lead Sponsor	Collaborator
National Center for Global Health and Medicine, Japan	Ministry of Health, Labour and Welfare, Japan

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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 plu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Virological efficacy	Virological efficacy of the group on DRV/r+RAL	48 weeks up to 96 weeks	Yes
Secondary	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	Yes
Secondary	Lipids	Triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol	48 weeks up to 96 weeks	Yes
Secondary	Adverse events	Adverse events of each arm, symptoms and rate	96 weeks	Yes
Secondary	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	Yes
Secondary	Discontinuation rate	Discontinuation rate of each arm, reason and timing	96 weeks	Yes