Diese Seite wurde automatisch übersetzt und die Genauigkeit der Übersetzung wird nicht garantiert. Bitte wende dich an die englische Version für einen Quelltext.

Safety and Effectiveness of Raltegravir Plus Darunavir/Ritonavir in Treatment-Naive HIV-Infected Adults

11. Oktober 2018 aktualisiert von: AIDS Clinical Trials Group

A Pilot Efficacy and Safety Trial of Raltegravir Plus Darunavir/Ritonavir for Treatment-Naive HIV-1-Infected Subjects

The purpose of this study is to assess the effectiveness and safety of an antiretroviral therapy (ART) regimen consisting of raltegravir (RAL) and darunavir (DRV)/ritonavir (RTV) as first-line therapy in treatment-naïve participants.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

Despite the remarkable strides made in the treatment of HIV-1-infected persons over the last decade, current first-line ART regimens are imperfect. The ideal combination, unlike some current first-line options, would have uncompromised efficacy in the presence of transmitted drug-resistant variants. The primary purpose of this study is to estimate the cumulative proportion of ART-naive participants experiencing virologic failure at or prior to week 24 after initiating raltegravir (RAL) plus darunavir/ritonavir (DRV/RTV).

The study will last 52 weeks. All participants will follow the same treatment schedule and take RAL plus DRV/RTV orally daily for the duration of the trial.

After entry, all participants will have scheduled visits at weeks 1, 4, 12, 24, 36, 48, and 52. Medical/medication history, blood and urine collection, and liver function tests will occur at screening. A targeted physical exam and concomitant medications history will occur at all study visits. Blood and urine collection and liver function tests will occur at most study visits. For females, a pregnancy test will occur at screening and study entry.

RAL and DRV were provided by the study. RTV was not provided by the study.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

113

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Vereinigte Staaten
    • Alabama
      • Birmingham, Alabama, Vereinigte Staaten, 35294
        • AlabamaTherapeutics CRS
    • California
      • Palo Alto, California, Vereinigte Staaten, 94304
        • Stanford CRS
      • San Diego, California, Vereinigte Staaten, 92103
        • Ucsd, Avrc Crs
      • San Francisco, California, Vereinigte Staaten, 94110
        • Ucsf Aids Crs
    • Colorado
      • Aurora, Colorado, Vereinigte Staaten, 80045
        • University of Colorado Hospital CRS
    • District of Columbia
      • Washington, District of Columbia, Vereinigte Staaten, 20007
        • Georgetown University CRS
    • Illinois
      • Chicago, Illinois, Vereinigte Staaten, 60611
        • Northwestern University CRS
    • Massachusetts
      • Boston, Massachusetts, Vereinigte Staaten, 02115
        • Beth Israel Deaconess Med Center
      • Boston, Massachusetts, Vereinigte Staaten, 02115
        • Brigham and Women's Hosp. ACTG CRS
    • Missouri
      • Saint Louis, Missouri, Vereinigte Staaten, 63110
        • Washington U CRS
    • New York
      • Rochester, New York, Vereinigte Staaten, 14604
        • AIDS Community Health Ctr. ACTG CRS
    • North Carolina
      • Chapel Hill, North Carolina, Vereinigte Staaten, 27599
        • Unc Aids Crs
      • Durham, North Carolina, Vereinigte Staaten, 27710
        • Duke Univ. Med. Ctr. Adult CRS
    • Ohio
      • Cincinnati, Ohio, Vereinigte Staaten, 45267-0405
        • Univ. of Cincinnati CRS
      • Cleveland, Ohio, Vereinigte Staaten, 44106
        • Case CRS
      • Cleveland, Ohio, Vereinigte Staaten, 44109
        • MetroHealth CRS
      • Columbus, Ohio, Vereinigte Staaten, 43210
        • The Ohio State Univ. AIDS CRS
    • Pennsylvania
      • Philadelphia, Pennsylvania, Vereinigte Staaten, 19104
        • Hosp. of the Univ. of Pennsylvania CRS
      • Pittsburgh, Pennsylvania, Vereinigte Staaten, 15213
        • University of Pittsburgh CTU
    • Rhode Island
      • Providence, Rhode Island, Vereinigte Staaten, 02906
        • The Miriam Hospital
    • Tennessee
      • Nashville, Tennessee, Vereinigte Staaten, 37203
        • Vanderbilt Therapeutics CRS
    • Texas
      • Houston, Texas, Vereinigte Staaten, 77030
        • Houston AIDS Research Team

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  • HIV-1-infected
  • Plasma HIV-1 RNA of at least 5,000 copies/mL within 90 days prior to study entry
  • HIV genotype (for reverse transcriptase and protease) performed at any time prior to study entry. More information on this criterion can be found in the protocol.
  • ARV drug-naive. More information on this criterion can be found in the protocol.
  • Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry
  • Agree to use one form of medically-accepted contraceptive throughout the study and for 60 days after stopping study treatment. More information on this criterion can be found in the protocol.

Exclusion Criteria:

  • Serious illness requiring systemic treatment and/or hospitalization for at least 7 days prior to study. More information on this criterion can be found in the protocol.
  • Screening HIV genotype obtained any time prior to study entry with more than one DRV resistance-associated mutation [RAM] (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, I84V, and L89V) or L76V alone
  • Known major integrase inhibitor RAM(s), including N155H, Q148H/R/K, Y143C/R, and G140S
  • Severe renal insufficiency requiring hemodialysis or peritoneal dialysis
  • Treatment with immunomodulators within 30 days prior to study entry. More information on this criterion can be found in the protocol.
  • Current medications that are prohibited with any study medications. More information on this criterion can be found in the protocol.
  • Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion.
  • Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with the study.
  • Certain abnormal laboratory results. More information on this criterion can be found in the protocol.
  • Pregnant or breastfeeding

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: N / A
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: RAL + DRV/RTV
Raltegravir (400 mg BID) plus Darunavir/Ritonavir (800 mg/100 mg QD) for 52 weeks
Arzneimittel: Raltegravir
400 mg tablet taken orally twice daily
Andere Namen:
  • RAL
Arzneimittel: Darunavir/Ritonavir
800 mg Darunavir/100 mg Ritonavir tablet taken orally once daily
Andere Namen:
  • DRV/RTV

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Proportion of Participants With Virologic Failure After Initiating RAL Plus DRV/RTV at or Prior to Week 24
Zeitfenster: From start of study treatment to week 24
Virologic failure is defined as: at week 12, confirmed plasma HIV-1 RNA >= 1000 copies/ml or confirmed rebound from the week 4 value by >0.5 log10 copies/ml (for subjects with week 4 value <= 50 copies/ml, confirmed rebound to >50 copies/ml); at week 24 or later, confirmed value > 50 copies/ml. Viral load confirmation was scheduled 7-35 days after initial virologic failure. The proportion was estimated using Kaplan-Meier method. An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.
From start of study treatment to week 24

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Proportion of Participants With Virologic Failure or Off Study Treatment Regimen or Death at or Prior to Week 24
Zeitfenster: From start of study treatment to Week 24
The proportion of participants with virologic failure (see primary outcome measure for definition) and/or premature treatment discontinuation/modification and/or death was estimated using Kaplan-Meier method. An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.
From start of study treatment to Week 24
Change in Plasma HIV-1 RNA From Baseline to Week 1
Zeitfenster: Baseline and week 1
Results report the week 1 change from baseline (week 1 - baseline) in HIV-1 RNA. Baseline HIV-1 RNA was computed as the mean of the log10 HIV-1 RNA values at pre-entry and study entry.
Baseline and week 1
Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/ml or <200 Copies/ml at Week 24
Zeitfenster: From start of study treatment to week 24
Results report the percentage of participants with plasma HIV-1 RNA < 50 copies/ml or <200 copies/ml at week 24.
From start of study treatment to week 24
Proportion of Participants With Plasma HIV-1 RNA <50 Copies/ml or <200 Copies/ml at Week 48
Zeitfenster: From start of study treatment to week 48
Results report the percentage of participants with plasma HIV-1 RNA <50 copies/ml or <200 copies/ml at week 48.
From start of study treatment to week 48
Proportion of Participants Who Experienced Signs/Symptoms or Laboratory Toxicities Grade 3 or Higher, or of Any Grade Which Led to a Permanent Change or Discontinuation of Study Treatment
Zeitfenster: From start of study treatment to week 52
Signs, symptoms and laboratory values were graded according to the Division of AIDS Adverse Event Grading System. Results report the percentage of participants who had grade 3 or higher events, or events of any grade which led to a permanent change or discontinuation of study treatment, which occurred any time from start of treatment to end of treatment.
From start of study treatment to week 52
Number of Participants With Pretreatment Drug Resistance
Zeitfenster: At screening
Results report the number of participants who had resistance to non-nucleoside reverse transciptase inhibitors (NNRTI), nucleoside reverse transciptase inhibitors (NRTI) and protease inbitors (PI) based on genotypic resistance testing done prior to participant's entry into the study. Participants are classified into one (and only one category) based on the maximum number of drug class resistance seen for the participant.
At screening
Number of Participants With Integrase Drug Resistance at Virologic Failure
Zeitfenster: From 12 weeks after starting study treatment to week 52
Results report the number of participants who had integrase resistance mutation(s) detected at the time of virologic failure.
From 12 weeks after starting study treatment to week 52
Number of Participants With Protease Drug Resistance at Virologic Failure
Zeitfenster: From 12 weeks after starting study treatment to week 52
Results report the number of participants who had protease resistance mutation(s) detected at the time of virologic failure.
From 12 weeks after starting study treatment to week 52
Number of Participants With Perfect Overall Adherence by Self Report
Zeitfenster: From one week after starting study treatment to week 52
At each study visit, adherence was measured in terms of the number of missed doses each participant had over a 4-day recall for each drug. Adherence for all study visit weeks were combined for an overall measure of adherence. Participants who had zero missed doses on all weeks in all drugs while on study were classified as having an overall "perfect" adherence.
From one week after starting study treatment to week 52
Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 24
Zeitfenster: From start of study treatment through week 24
Results report the week 24 change from week 0 (week 24 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.
From start of study treatment through week 24
Change in Fasting Low-density Lipoprotein at Week 24
Zeitfenster: From start of study treatment through week 24
Results report the week 24 change from week 0 (week 24 - week 0) fasting low-density lipoprotein (LDL). For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used. Direct fasting LDL was reported when the participant had high fasting triglyceride.
From start of study treatment through week 24
Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 48
Zeitfenster: From start of study treatment through week 48
Results report the week 48 change from week 0 (week 48 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.
From start of study treatment through week 48
Change in Fasting Low-density Lipoprotein at Week 48
Zeitfenster: From start of study treatment through week 48
Results report the week 48 change from week 0 (week 48 - week 0) fasting low-density lipoprotein (LDL). For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used. Direct fasting LDL was reported when the participant had high fasting triglyceride.
From start of study treatment through week 48
Change in CD4 Count at Week 48
Zeitfenster: From start of study treatment through week 48
Results report the week 48 change from baseline (week 48 - baseline) in CD4 count. Baseline CD4 count was computed as the mean of CD4 count values at pre-entry and study entry.
From start of study treatment through week 48
Plasma Trough Concentration of Raltegravir
Zeitfenster: From start of study treatment to week 52
Plasma trough concentrations (ng/ml) of Raltegravir (RAL) below the detection limit (10 ng/ml) were replaced by half the corresponding lower limit of quantitation. Geometric mean of trough concentrations obtained within the prescribed trough time (within 9-15 hours after the last RAL dose) was computed for each participant. For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.
From start of study treatment to week 52
Plasma Trough Concentration of Darunavir
Zeitfenster: From start of study treatment to week 52
Plasma trough concentrations (ng/ml) of Darunavir (DRV) below the detection limit (50 ng/ml) were replaced by half the corresponding lower limit of quantitation. Geometric mean of trough concentrations obtained within the prescribed trough time (within 20-28 hours after the last DRV dose) was computed for each participant. For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.
From start of study treatment to week 52

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

AIDS Clinical Trials Group

Mitarbeiter

National Institute of Allergy and Infectious Diseases (NIAID)

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. April 2009

Primärer Abschluss (Tatsächlich)

1. Februar 2010

Studienabschluss (Tatsächlich)

1. September 2010

Studienanmeldedaten

Zuerst eingereicht

26. Januar 2009

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

27. Januar 2009

Zuerst gepostet (Schätzen)

28. Januar 2009

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

8. November 2018

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

11. Oktober 2018

Zuletzt verifiziert

1. Oktober 2018

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • ACTG A5262
  • 1U01AI068636 (US NIH Stipendium/Vertrag)

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

Klinische Studien zur HIV-1-Infektionen

Klinische Studien zur Raltegravir

Suchen Sie nach ähnlichen Studien

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

CROs by country

CROs in Cambodia

Bedingungen

Seltene Krankheiten

Drogeninterventionen

Nahrungsergänzungsmittel

Sponsor / Mitarbeiter

Standorte

3
Abonnieren