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HIVPhase 3NCT00381303

GRACE: A Study to Compare the Effectiveness, Safety and Tolerability of PREZISTA (Darunavir)/Ritonavir by Gender and Race When Administered With Other Antiretroviral Medications in Human Immunodeficiency Virus (HIV) Positive Women and Men.

A Phase 3 study testing darunavir and ritonavir in people with HIV and Infectious, run by Tibotec, Inc at 46 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate any differences in the effectiveness, safety, and tolerability of PREZISTA (darunavir; DRV) 600 mg, administered with ritonavir (RTV) 100 mg twice a day on virologic response (defined as a viral load (VL) of < 50 copies/mL) over a 48-week treatment period in HIV-positive women… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV, Infectious
What is being tested?
darunavir and ritonavir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
429 participants
Where
46 sitesin 3 countries
Study dates
Nov 2006to Dec 2008
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented HIV infection
  • Plasma HIV-RNA >= 1000 copies/mL
  • Must be able to comply with protocol requirements

Who cannot join

  • No prior use of PREZISTA (darunavir), TMC125, enfuvirtide, or tipranavir
  • No currently active AIDS defining illness, Category C conditions according to the Center for Disease Control [CDC] Classification System for HIV Infection (1993) with the following exceptions, which must be discussed with the Sponsor prior to enrollment: stable cutaneous Kaposi's Sarcoma, Wasting syndrome due to HIV infection
  • Not currently using an investigational drug
  • Not pregnant or breastfeeding
  • No Grade 3 or 4 laboratory abnormality as defined by DAIDS (Division of AIDS, National Institute of Allergy and Infectious Diseases).

Trial locations and contacts

46 sites in 3 countries.

46 sites in 3 countries

United States41 sites

  • Study site

    Atlanta, Georgia

  • Study site

    Austin, Texas

  • Study site

    Baltimore, Maryland

  • Study site

    Birmingham, Alabama

  • Study site

    Boston, Massachusetts

  • Study site

    Chapel Hill, North Carolina

  • Study site

    Charlottesville, Virginia

  • Study site

    Chicago, Illinois

  • Study site

    Cincinnati, Ohio

  • Study site

    Dallas, Texas

  • Study site

    Detroit, Michigan

  • Study site

    Durham, North Carolina

  • Study site

    Fort Lauderdale, Florida

  • Study site

    Harlingen, Texas

  • Study site

    Houston, Texas

  • Study site

    Jacksonville, Florida

  • Study site

    Kansas City, Kansas

  • Study site

    Longview, Texas

  • Study site

    Los Angeles, California

  • Study site

    Miami, Florida

  • Study site

    Neptune City, New Jersey

  • Study site

    New Orleans, Louisiana

  • Study site

    New York, New York

  • Study site

    Newark, New Jersey

  • Study site

    North Palm Beach, Florida

  • Study site

    Orlando, Florida

  • Study site

    Pensacola, Florida

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Phoenix, Arizona

  • Study site

    Port Saint Lucie, Florida

  • Study site

    Sacramento, California

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    Savannah, Georgia

  • Study site

    Springfield, Massachusetts

  • Study site

    St Louis, Missouri

  • Study site

    The Bronx, New York

  • Study site

    Torrance, California

  • Study site

    Washington D.C., District of Columbia

  • Study site

    West Palm Beach, Florida

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

Canada3 sites

  • Study site

    Hamilton, Ontario

  • Study site

    Montreal, Quebec

  • Study site

    Toronto, Ontario

Other trials in Canada

Puerto Rico2 sites

  • Study site

    Ponce, PR

  • Study site

    Rio Piedras

Other trials in Puerto Rico

About this study

Official title: GRACE: An Open-label, Multicenter Trial to Compare the Efficacy, Safety, and Tolerability of PREZISTA (Darunavir)/Ritonavir by Gender and Race, When Administered in Combination With an Individually Optimized Background Regimen Over a 48-week Treatment Period.

The purpose of this study is to evaluate any differences in the effectiveness, safety, and tolerability of PREZISTA (darunavir; DRV) 600 mg, administered with ritonavir (RTV) 100 mg twice a day on virologic response (defined as a viral load (VL) of < 50 copies/mL) over a 48-week treatment period in HIV-positive women and men. Additional antiretroviral (ARV) agents will also be administered and will be chosen by the Investigator based on resistance testing and prior treatment history (referred to as the Optimized Background Regimen (OBR)).

Read the detailed description

This is a multi-center, open-label (doctors and patients know which drug is being administered), Phase IIIb clinical trial to evaluate differences in effectiveness, safety, and tolerability of darunavir/ritonavir by sex and/or race over a 48-week treatment period. This study will be conducted in HIV positive women and men who have been treated previously with antiretroviral therapy. This study will enroll 70% women and will be conducted in the U.S., Puerto Rico, Mexico and Canada in approximately 420 patients who will receive darunavir 600 mg and ritonavir 100 mg twice daily. The primary objective of this study is to determine the percentage of patients who achieve virologic response, defined as a viral load (VL) of <50 copies/mL at week 48. Secondary study objectives include comparisons of endpoints between women and men as well as race across multiple parameters including but not limited to change in CD4 count from baseline to week 48, time to loss of virologic response (TLOVR), changes in metabolic parameters (blood chemistry), etc.

Within 4 weeks after the Screening Visit (initial visit with investigator to determine eligibility), the Investigator should have received all data required to determine the patient's eligibility and will construct the individual Optimized Background Regimen (OBR) that will be used during the treatment period in combination with darunavir/ritonavir for those patients enrolled in the study. The OBR will consist of additional antiretroviral (ARV) agents that will also be administered during the study chosen by the Investigator and based on resistance testing and prior treatment history. The study Sponsor will provide the following ARV agents, that may be used as options for the OBR: TMC 125 (investigational non-nucleoside reverse transcriptase inhibitor; NNRTI); Truvada (tenofovir/emtricitabine); Viread (tenofovir); Emtriva (emtricitabine); Zidovudine. Other NRTIs (nucleoside reverse transcriptase inhibitors) or NNRTIs may be used at the discretion of the Investigator, but will not be provided by the Sponsor. The Baseline Visit (Day 1) will be followed by a 48-week treatment period during which patients will be evaluated at Weeks 4, 8, 12, 16, 24, 36, 48 and at a final Follow-Up Visit during Week 52. (total of 10 visits from Screening to final visit). At a number of visits throughout the study, blood samples will be obtained to assess defined laboratory values, safety parameters and to determine concentrations of study drugs darunavir, TMC125 (if applicable) and ritonavir). Patients will be assessed for change in CD4 count and HIV-RNA throughout the study. At each visit, vital signs will be assessed and patients will be asked about any untoward medical occurrences and these will be recorded as adverse events (AEs) and/or HIV-related events. Detailed definitions and reporting procedures for AEs will be provided as part of the protocol. Study patients will receive PREZISTA (darunavir) 600 mg boosted with 100 mg of ritonavir orally (by mouth) twice a day in combination with other antiretroviral drugs for 48 weeks.

Conditions
HIV, Infectious
Being tested
darunavir, ritonavir
Keywords
HIV, AIDS, Immunodeficiency Virus, Human, Females, Women, PREZISTA, darunavir, TMC114, Protease Inhibitor
Medical subject headings
Communicable Diseases, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • darunavirDrug

    600mg bid for 48 wks

  • ritonavirDrug

    100mg bid for 48 wks

Study groups in NCT00381303
Study groupRoleWhat they receive
001Experimentaldarunavir 600mg bid for 48 wks,ritonavir 100mg bid for 48 wks
Receives: Drug: darunavir; Drug: ritonavir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Viral Load (VL) < 50 HIV-1 RNA Copies/mL (Time to Loss of Virologic Response[TLOVR]) Subjects by Sex

    TLOVR - responders/non-responders per FDA TLOVR response algorithm. A subject was considered a responder at that time point and that subsequent. A subject was considered a non-responder at a time point in the following situations: discontinued treatment at that time point, a rebound value at that time point and that subsequent or at that time point and that followed by treatment discontinuation, intermittent missing values were considered a response if the immediately preceding and following visits were a response, rebound at earlier time point, or any new, unplanned ARV except in tolerability

    Measured: Week 48

  2. Number of TLOVR Non-virologic Failure (VF) Censored - VL < 50 HIV-1 RNA Subjects by Sex

    TLOVR non-virologic failure (VF) censored. This imputation method differs from the TLOVR algorithm, because subjects that dropped out for reasons other than virologic failure were censored from the time of discontinuation onwards.

    Measured: Week 48

Secondary outcomes (8)

  1. Number of VL < 50 HIV-1 RNA Copies/mL (TLOVR) Subjects by Race

    Intention to Treat population (ITT)

    Measured: Week 48

  2. Number of Etravirine-TMC125 (ETR) Subgroup- VL < 50 HIV-1 RNA Copies/mL (TLOVR) Subjects

    The Etravirine-TMC125 (ETR Subgroup population was defined as all ITT subjects who took at least 1 dose of ETR)

    Measured: Week 48

  3. Descriptive Statistics of [TLOVR Non-virologic Failure (VF) Censored] - VL < 50 HIV-1 RNA by Race

    TLOVR non-virologic failure (VF) censored. This imputation method differs from the TLOVR algorithm, because subjects that dropped out for reasons other than virologic failure were censored from the time of discontinuation onwards.

    Measured: Week 48

  4. Descriptive Statistics of ETR Subgroup [TLOVR Non-virologic Failure (VF) Censored] - VL < 50 HIV-1 RNA

    The Etravirine-TMC125 (ETR Subgroup population was defined as all ITT subjects who took at least 1 dose of ETR)

    TLOVR non-virologic failure(VF) censored. This imputation method differs from the TLOVR algorithm, because subjects that dropped out for reasons other than virologic failure were censored from the time of discontinuation onwards.

    Measured: Week 48

  5. Descriptive Statistics of Change From Baseline in CD4+ Cell Count Using Observed Values

    Observed obsevations have no imputation methods applied.

    Measured: Baseline, Week 48

  6. Descriptive Statistics of ETR Subgroup - Change From Baseline in CD4+ Cell Using Observed Values

    The Etravirine-TMC125 (ETR Subgroup population was defined as all ITT subjects who took at least 1 dose of ETR)

    Measured: Week 48

  7. Descriptive Statistics of Change From Baseline in CD4+ Cell Count Using the Imputation Method of Last Observation Carried Forward (LOCF)

    Last Observation Carried Forward (LOCF) imputation method applied.

    Measured: Week 48

  8. Descriptive Statistics of ETR Subgroup - Change From Baseline in CD4+ Cell Count Using the Imputation Method of LOCF

    The Etravirine-TMC125 (ETR Subgroup population was defined as all ITT subjects who took at least 1 dose of ETR). The Last Observation Carried Forward (LOCF) imputation method was applied.

    Measured: Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2006 (estimated)
  2. Study startNov 2006
  3. Primary completionNov 2008
  4. Study completionDec 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
429 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00381303
Sponsor's protocol ID
CR011869
Other IDs
TMC114HIV3004
Status last verified
Apr 2014
First submitted
26 Sep 2006
Last updated
21 Apr 2014
Data monitoring committee
Yes

Publications

  • Tsoukas C, Gilbert L, Lewis T, Hatzakis G, Falcon R, Mrus J. Improvements in Immune Function and Activation with 48-Week Darunavir/Ritonavir-Based Therapy: GRACE Substudy. ISRN AIDS. 2013 Dec 12;2013:358294. doi: 10.1155/2013/358294. eCollection 2013.

    PubMed 24396625

  • Smith KY, Garcia F, Kumar P, Currier JS, Ryan R, Falcon R, Mrus J, Squires K. Assessing darunavir/ritonavir-based therapy in a racially diverse population: 48-week outcomes from GRACE. J Natl Med Assoc. 2012 Jul-Aug;104(7-8):366-76. doi: 10.1016/s0027-9684(15)30179-6.

    PubMed 23092052

  • Currier J, Averitt Bridge D, Hagins D, Zorrilla CD, Feinberg J, Ryan R, Falcon R, Tennenberg A, Mrus J, Squires K; GRACE (Gender, Race, And Clinical Experience) Study Group. Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial. Ann Intern Med. 2010 Sep 21;153(6):349-57. doi: 10.7326/0003-4819-153-6-201009210-00002.

    PubMed 20855799

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing darunavir and ritonavir in people with HIV and Infectious, run by Tibotec, Inc at 46 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in United States, Canada, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Viral Load (VL) < 50 HIV-1 RNA Copies/mL (Time to Loss of Virologic Response[TLOVR]) Subjects by Sex (time frame: Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00381303, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2014.

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Clinical Trial NCT00381303 | AzTrials