UMIN-CTR Clinical Trial

Public title

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

Acronym

SPARE Study

Scientific Title

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

Scientific Title:Acronym

SPARE Study

Region

Japan

Condition

HIV infections, AIDS, HIV-1

Classification by specialty

Infectious disease

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The main objective of this trial to randomize HIV infected patients under good HIV control with tenofovir (TDF), emtricitabine (or lamivudine) and lopinavir/ritonavir (LPV/r) into an arm continuing the ongoing regimen or the other arm switching the regimen to raltegravir (RAL) with darunavir/ritonavir (DRV/r) 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 the patients' renal functions and has the same virological efficacy in comparison with a standard treatment with TDF, or not.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

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 study.

Key secondary outcomes

1) Virological efficacy of the group on DRV/r+RAL (after 48 weeks and up to 96 weeks)
2) 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)
3) Comparison of lipid markers between the two arms: triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol (after 48 weeks and up to 96 weeks)
4) Discontinuation rate of each arm, reason and timing of the discontinuation or the treatment change up to 96 weeks
5) Adverse events of each arm, symptoms and rate up to 96 weeks
6) Blood plasma concentration level of RAL and DRV of all consented intervened cases at National Center for Global Health and Medicine

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

An arm to change the regimen 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, Norvir soft-capsule 1 cap PC BID, and Isentress 1 tab PC BID

(Norvir soft-capsule may be substituted by Notvir tablet upon consultation)

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

Interventions/Control_2

An arm continuing on as 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 and Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

HIV infected outpatients or inpatients that are:
1) without history virological failure including protease inhibitors or raltegravir (disregarding whether the patient had a history of drug resistance or drug holiday, or not)
2) taking LPV/r+TVD (or TDF+lamivudine) for longer than 15 weeks before the enrollment
3) 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).
4) 20 years old or older
5) Japanese
6) willing to participate in the trial and able to agree to the informed consent.

Key exclusion criteria

Cases applicable to any of the following will be excluded from this trial:
1) HBs antigen positive within 15 weeks to the enrollment (cases confirmed as HBs antibody positive can be enrolled without HBs antigen testing)
2) Malabsorption or gastrointestinal symptoms that affect absorption of the drugs, or dysphagia cases
3) Clinical data within 15 weeks before the start of the trial and of the closest date to the enrollment that are:
a. GPT 2.5 times the highest of the normal range (grade 2)
b. eGFR less than 60ml/min (Cockcroft-Gault formula)
4) Cases with opportunistic infections requiring treatment (primary and secondary preventive prophylaxis can be administrated during the study)
5) Cases during pregnancy or nursing period, or with a possibility for pregnancy
6) Using drugs that are prohibited to combine for drug interaction with the drugs of this trial
7) Other cases that are decided by the patient's physician as not suitable for the trial

Target sample size

54

Name of lead principal investigator

1st name
Middle name
Last name	Shinichi Oka

Organization

National Center for Global Health and Medicine

Division name

AIDS Clinical Center

Zip code

Address

1-21-1 Toyama, Shinjuku, Tokyo JAPAN

TEL

03-5273-5193

Email

oka@acc.ncgm.go.jp

Name of contact person

1st name
Middle name
Last name	Takeshi Nishijima

Organization

National Center for Global Health and Medicine

Division name

AIDS Clinical Center

Zip code

Address

1-21-1 Toyama, Shinjuku, Tokyo JAPAN

TEL

03-3202-7181(5673)

Homepage URL

Email

tnishiji@acc.ncgm.go.jp

Institute

AIDS Clinical Center at National Center for Global Health and Medicine

Institute

Department

Personal name

Organization

Ministry of Health, Labour and Welfare (Japan)

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

NCT01294761

Org. issuing International ID_1

National Institutes of Health (NIH)

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

独立行政法人国立国際医療研究センター病院（東京都）

Date of disclosure of the study information

2011

Year

02

Month

21

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2011

Year

01

Month

27

Day

Date of IRB

Anticipated trial start date

2011

Year

02

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2011

Year

02

Month

21

Day

Last modified on

2014

Year

02

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006083