このページは自動翻訳されたものであり、翻訳の正確性は保証されていません。を参照してください。 英語版 ソーステキスト用。

Prospective Evaluation of Anti-retroviral Combinations for Treatment Naive, HIV Infected Persons in Resource-limited Settings (PEARLS)

2018年9月11日 更新者：AIDS Clinical Trials Group

Randomized, Open-Label Evaluation of Efficacy of Once-Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Persons From Resource-Limited Settings (PEARLS) Trial

This study compared 3 different three-drug combinations in HIV infected individuals starting their first HIV treatment regimens. Participants were recruited from resource-limited areas in Africa, Asia, South America, Haiti, and also from the United States. The study hypothesis was each of the once daily combinations (PI based, or NNRTI based) would not have inferior efficacy compared to the twice daily NNRTI based combination.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

In developed countries, standard effective antiretroviral (ARV) therapy for treatment-naive HIV infected people includes three-drug combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, direct comparisons of ARV efficacy in persons that more closely reflect the worldwide demographics of HIV-1 infection are needed.> > Trial participants were recruited in Africa (Malawi, South Africa, Zimbabwe), Asia (India, Thailand), South America (Brazil, Peru), Haiti, and the United States.>

> All participants were randomly assigned to one of three arms, and random allocation was stratified by 2 factors: country, and screening plasma HIV-1 RNA level (< 100,000 copies/mL versus >= 100,000 copies/mL). Participants assigned to the ZDV/3TC+EFV arm received lamivudine/zidovudine twice daily and efavirenz once daily. Participants assigned to the ddI+FTC+ATV arm received emtricitabine, atazanavir, and enteric-coated didanosine once daily. Participants assigned to the TDF/FTC+EFV arm received emtricitabine, tenofovir disoproxil fumarate, and efavirenz once daily. >

>

> Physical exam and blood collection occurred at entry and at most study visits. Participants experiencing virologic failure were offered a switch to another regimen. >

> On May 23, 2008, the ddI+FTC+ATV was closed following a planned interim review by the study's independent Data and Safety Monitoring Board (DSMB). The DSMB recommendation was based upon compelling evidence that this arm had significantly more virologic failure (and therefore was inferior when) compared to the ZDV/3TC+EFV arm . Participants still receiving ddI+FTC+ATV were offered alternative medications, and all participants continued to be followed. >

> On November 3, 2009, the DSMB recommended that the study close to all follow-up on May 31, 2010, before the designed termination (based on 30% of participants meeting the primary outcome) was met. The board observed that the recent accumulation of primary efficacy events (i.e. regimen failures) was very slow. Therefore, if the study were to continue another 1-2 years, the precision gained for treatment comparisons would likely be small.

研究の種類

介入

入学 (実際)

1571

段階

  • フェーズ 4

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • California
      • Los Angeles、California、アメリカ、90033-1079
        • University of Southern California
      • Los Angeles、California、アメリカ、90095-1793
        • UCLA CARE Center CRS
      • Torrance、California、アメリカ、90502-2052
        • Harbor General/UCLA
    • Colorado
      • Denver、Colorado、アメリカ
        • Univ. of Colorado Health Sciences Center, Denver
    • Hawaii
      • Honolulu、Hawaii、アメリカ、96816-2396
        • Univ. of Hawaii at Manoa, Leahi Hosp.
    • Illinois
      • Chicago、Illinois、アメリカ、60611-3015
        • Northwestern University
      • Chicago、Illinois、アメリカ、60612
        • Cook County Hospital Core Center
      • Chicago、Illinois、アメリカ、60612-3806
        • Rush-Presbyterian/St. Lukes (Chicago)
    • Minnesota
      • Minneapolis、Minnesota、アメリカ、55455-0392
        • University of Minnesota
    • Missouri
      • Saint Louis、Missouri、アメリカ、63108-2138
        • Washington University (St. Louis)
    • New York
      • HVTN 722 West 168th Street MSPH Bldg.、New York、アメリカ、10032
        • HIV Prevention & Treatment CRS
      • New York、New York、アメリカ、10003
        • Beth Israel Medical Center
      • New York、New York、アメリカ、10016
        • NY Univ. HIV/AIDS CRS
      • New York、New York、アメリカ、10011
        • Cornell CRS
      • Rochester、New York、アメリカ、14642-0001
        • Univ. of Rochester ACTG CRS
      • Rochester、New York、アメリカ、14642-0001
        • Community Health Network, Inc.
    • North Carolina
      • Chapel Hill、North Carolina、アメリカ、27514
        • University of North Carolina
      • Chapel Hill、North Carolina、アメリカ、27514
        • Wake County Health and Human Services Clinical Research Site
      • Durham、North Carolina、アメリカ、27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati、Ohio、アメリカ、45267-0405
        • University of Cincinnati
      • Columbus、Ohio、アメリカ、43210
        • The Ohio State Univ. AIDS CRS
    • Pennsylvania
      • Philadelphia、Pennsylvania、アメリカ、19104
        • Hosp. of the Univ. of Pennsylvania CRS
    • Rhode Island
      • Providence、Rhode Island、アメリカ、02906
        • The Miriam Hosp. ACTG CRS
      • Providence、Rhode Island、アメリカ、02906
        • Stanley Street Treatment and Resource
    • Tennessee
      • Nashville、Tennessee、アメリカ、37204
        • Vanderbilt Therapeutics CRS
    • Texas
      • Dallas、Texas、アメリカ
        • University of Texas, Southwestern Medical Center
      • Galveston、Texas、アメリカ、77555-0435
        • University of Texas, Galveston
  • インド
      • Pune、インド、411026
        • Dr. Kotnis Dispensary
    • Chennai
      • Rajiv Gandhi Salai Taramani、Chennai、インド、600113
        • YRG CARE Medical Ctr., VHS Chennai CRS
    • Maharashtra
      • Pune、Maharashtra、インド
        • NARI Pune CRS
    • Pune
      • Maharashtra State、Pune、インド
        • NARI Clinic at NIV CRS
  • ジンバブエ
    • Harare
      • AIDS Research Unit P.O. Box A178、Harare、ジンバブエ
        • UZ-Parirenyatwa CRS
  • タイ
    • Chiang Mai
      • P.O. Box 80、Chiang Mai、タイ、50200
        • Chiang Mai Univ. ACTG CRS
  • ハイチ
    • Port-au-Prince
      • Bicentenaire、Port-au-Prince、ハイチ、HT-6110
        • Les Centres GHESKIO CRS
  • ブラジル
    • RS
      • Porto Alegre、RS、ブラジル、91350-200
        • Hospital Nossa Senhora da Conceicao
    • Rio De Janeiro
      • Manguinhos、Rio De Janeiro、ブラジル
        • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
  • ペルー
    • Lima
      • Barranco、Lima、ペルー
        • Asociacion Civil Impacta Salud y Educacion - Miraf CRS
      • San Miguel、Lima、ペルー
        • San Miguel CRS
  • マラウイ
    • Blantyre
      • P.O. Box 1131、Blantyre、マラウイ
        • College of Med. JHU CRS
    • Lilongwe
      • Mzimba Road、Lilongwe、マラウイ
        • University of North Carolina Lilongwe CRS
  • 南アフリカ
    • Gauteng
      • Johannesburg、Gauteng、南アフリカ、2092
        • Wits HIV CRS
    • KwaZulu Natal
      • Durban、KwaZulu Natal、南アフリカ、4001
        • Durban Adult HIV CRS

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria :>

  • HIV-1 infected>
  • CD4 count fewer than 300 cells/mm3 >
  • Viral load test result>
  • Absolute Neutrophil Count at least 750mm3 >
  • Hemoglobin at least 7.5 g/dL>
  • Platelet count at least 50,000/mm3>
  • Calculated creatinine clearance at least 60 mL/min>
  • A , A, and alkaline phosphatase <= 5 times upper limit of normal>
  • total bilirubin <= 2.5 times upper limit of normal>
  • Karnofsky performance score of 70 or higher>
  • Plans to stay in the area for the duration of the study>
  • Agrees to use acceptable forms of contraception for the duration of the study>

Exclusion Criteria:>

  • More than 7 days exposure to ARVs (except for single-dose NVP or ZDV for any period for the purpose of pMTCT)>
  • Acute therapy for serious medical illnesses within 14 days prior to study entry>
  • Certain abnormal laboratory values>
  • Radiation therapy or chemotherapy within 45 days prior to study entry. >
  • Any immunomodulator, HIV vaccine, or other investigational therapy within 30 days prior to study entry. >
  • Current alcohol or drug abuse that, in the opinion of the site investigator, would interfere with study participation>
  • Inflamed pancreas within 3 years prior to study entry>
  • Allergy/sensitivity to any of the study drugs or their formulations>
  • Heart rate less than 40 beats/min>
  • History of untreated, active second- or third-degree heart block>
  • Currently detained in jail or for treatment of a psychiatric or physical illness>
  • Vomiting or inability to swallow medications>
  • Pregnancy>

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：ZDV/3TC+EFV
ZDV/3TC+EFV participants will receive lamivudine/zidovudine and efavirenz
薬：Efavirenz
600 mg taken orally daily
他の名前：
  • EFV
薬：Lamivudine/Zidovudine
150 mg/300 mg taken orally twice daily
他の名前：
  • 3TC/ZDV
実験的：ddI+FTC+ATV
ddI+FTC+ATV participants will receive emtricitabine, atazanavir, and enteric-coated didanosine
薬：Atazanavir
400 mg taken orally daily
他の名前：
  • テレビ
薬：Didanosine (enteric-coated)
400 mg taken orally daily
他の名前：
  • ddI
薬：Emtricitabine
200 mg taken orally daily
他の名前：
  • FTC
実験的：TDF/FTC+EFV
TDF/FTC+EFV participants will receive emtricitabine/tenofovir disoproxil fumarate and efavirenz
薬：Efavirenz
600 mg taken orally daily
他の名前：
  • EFV
薬：Emtricitabine/Tenofovir disoproxil fumarate
200 mg/300 mg taken orally once daily
他の名前：
  • FTC/TDF

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Time to Treatment Failure (PI Comparison)
時間枠：Virologic failure starting 14 weeks following randomization; disease progression starting 12 weeks following randomization; and death occurring at any time following randomization. Follow-up until ddI+FTC+ATV arm closed (May 22, 2008).
Time from randomization to the earliest of: scheduled week of first plasma sample meeting virologic failure (two consecutive plasma HIV-1 RNA values 1,000 copies/mL or higher, regardless of whether ARV medications being taken at the time); scheduled week of first AIDS defining diagnosis (WHO Stage 4 (2005), plus microsporidiosis, cyclospora gastroenteritis and Chaga's disease), not attributed to Immune Reconstitution Inflammatory Syndrome (reviewed by chairs); date of death (due to any cause). Plasma drawn every 8 weeks (except confirmation samples could be drawn earlier).
Virologic failure starting 14 weeks following randomization; disease progression starting 12 weeks following randomization; and death occurring at any time following randomization. Follow-up until ddI+FTC+ATV arm closed (May 22, 2008).
Time to Treatment Failure (NRTI Comparison)
時間枠：Virologic failure starting 14 weeks following randomization; disease progression starting 12 weeks following randomization; and death occurring at any time following randomization. Follow-up through study closure (May 31, 2010).
Time from randomization to the earliest of: scheduled week of first plasma sample meeting virologic failure (two consecutive plasma HIV-1 RNA values 1,000 copies/mL or higher, regardless of whether ARV medications being taken at the time); scheduled week of first AIDS defining diagnosis (WHO Stage 4 (2005) plus microsporidiosis, cyclospora gastroenteritis and Chaga's disease), not attributed to Immune Reconstitution Inflammatory Syndrome (reviewed by chairs); date of death (due to any cause). Plasma drawn every 8 weeks (except confirmation samples could be drawn earlier).
Virologic failure starting 14 weeks following randomization; disease progression starting 12 weeks following randomization; and death occurring at any time following randomization. Follow-up through study closure (May 31, 2010).

二次結果の測定

結果測定
メジャーの説明
時間枠
Time to Discontinuation of Initial Antiretroviral (ARV) Therapy (PI Comparison)
時間枠：Throughout follow-up until ddI+FTC+ATV arm closed (May 22,2008)
Time is measured from date of treatment initiation to earliest of the following: date of last participant contact (premature discontinuation of study follow-up); date all ARV medications were held (if all medications held for at least 8 weeks, for any reason); date that any ARV medication was changed (excluding the following single ARV substitutions: stavudine or tenofovir for zidovudine, nevirapine for efavirenz, or didanosine for tenofovir).
Throughout follow-up until ddI+FTC+ATV arm closed (May 22,2008)
Time to Immunologic Failure (PI Comparison)
時間枠：At or after Week 48 (including only follow-up until ddI+FTV+ATV arm closed - May 22,2008)
Time from randomization to the first scheduled study visit (week 48 or later) with a CD4+ cell count fewer than 100 cells/mm3.
At or after Week 48 (including only follow-up until ddI+FTV+ATV arm closed - May 22,2008)
Change in CD4 Count From Screening to Weeks 24, 48, 96 (PI Comparison)
時間枠：weeks 24, 48 and 96 (including follow-up until ddI+FTC+ARV arm closed - May 22, 2008)
Available pre-randomization CD4 cell counts were limited to the single CD4 cell count used for study eligibility (and therefore must have been fewer than 300 cells/mm3).
weeks 24, 48 and 96 (including follow-up until ddI+FTC+ARV arm closed - May 22, 2008)
Time to First Dose Modification or Grade 3 or 4 Adverse Event (PI Comparison)
時間枠：Throughout study follow-up until ddI+FTC+ATV arm closed (May 22, 2008)
Time from treatment dispensation to the first occurring of the following: week of first ARV medication change; week of first grade 3 or higher sign/symptom or laboratory abnormality (total bilirubin was excluded) that was at least one grade higher than baseline. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.
Throughout study follow-up until ddI+FTC+ATV arm closed (May 22, 2008)
Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml (PI Comparison)
時間枠：At Weeks 24 and 48 (including only follow-up until ddI+FTC+ARV arm closed - May 22, 2008)
Number of participants with plasma HIV-1 Viral load fewer than 400 copies/mL at study visit weeks 24 and 48. Closest observed result between 20 and up to 28 weeks (for week 24), and between 44 and up to 52 (for week 48) used if multiple results available. Missing values excluded, and both study treatment status and history ignored.
At Weeks 24 and 48 (including only follow-up until ddI+FTC+ARV arm closed - May 22, 2008)
Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm - Excluding Study Allowed ARV Substitutions)(PI Comparison)
時間枠：Week 48 (using follow-up only until closing of ddI+FTV+ATV arm on May 22,2008)
Time from randomization to any of the following events occurring prior to week 48: discontinued ARV regimen (see time to discontinuation of initial ARV therapy above); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values < 400 copies/mL; two consecutive plasma HIV-1 RNA values > 400 copies/mL following virologic suppression.
Week 48 (using follow-up only until closing of ddI+FTV+ATV arm on May 22,2008)
Time to Loss of Virologic Response at Week 48 (Defined by FDA TLOVR Algorithm - Including All ARV Substitutions)(PI Comparison)
時間枠：Week 48 (using follow-up only until closing of ddI+FTV+ATV arm on May 22,2008)
Time from randomization to any of the following events occurring prior to week 48: changed any ARV medication (including permanent discontinuation of all medications); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values < 400 copies/mL; two consecutive plasma HIV-1 RNA values > 400 copies/mL following virologic suppression.
Week 48 (using follow-up only until closing of ddI+FTV+ATV arm on May 22,2008)
Time to Discontinuation of Initial Antiretroviral (ARV) Therapy (NRTI Comparison)
時間枠：Throughout follow-up until study closed (May 31,2010)
Time is measured from date of treatment initiation to earliest of the following: date of last participant contact (premature discontinuation of study follow-up); date all ARV medications were held (if all medications held for at least 8 weeks, for any reason); date that any ARV medication was changed (excluding the following single ARV substitutions: stavudine or tenofovir for zidovudine, nevirapine for efavirenz, or didanosine for tenofovir).
Throughout follow-up until study closed (May 31,2010)
Time to Immunologic Failure (NRTI Comparison)
時間枠：At or after Week 48 (including all follow-up through study closure - May 31,2010)
Time from randomization to the first scheduled study visit (week 48 or later) with a CD4+ cell count fewer than 100 cells/mm3.
At or after Week 48 (including all follow-up through study closure - May 31,2010)
Change in CD4 Count From Screening to Weeks 24, 48, 96 (NRTI Comparison)
時間枠：weeks 24, 48 and 96 (including all follow-up through to study closure on May 31, 2010)
Available pre-randomization CD4 cell counts were limited to the single CD4 cell count used for study eligibility (and therefore must have been fewer than 300 cells/mm3).
weeks 24, 48 and 96 (including all follow-up through to study closure on May 31, 2010)
Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml (NRTI Comparison)
時間枠：At Weeks 24 and 48 (including follow-up through to study closure on May 31, 2010)
Number of participants with plasma HIV-1 Viral load fewer than 400 copies/mL at study visit weeks 24 and 48. Closest observed result between 20 and up to 28 weeks (for week 24), and between 44 and up to 52 (for week 48) used if multiple results available. Missing values excluded, and both study treatment status and history ignored.
At Weeks 24 and 48 (including follow-up through to study closure on May 31, 2010)
Time to Loss of Virologic Response at Week 48 (Defined by FDA TLOVR Algorithm - Excluding Study Allowed ARV Substitutions)(NRTI Comparison)
時間枠：Week 48 (using follow-up through study closure on May 31,2010)
Time from randomization to any of the following events occurring prior to week 48: discontinued ARV regimen (see time to discontinuation of initial ARV therapy above); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values < 400 copies/mL; two consecutive plasma HIV-1 RNA values > 400 copies/mL following virologic suppression.
Week 48 (using follow-up through study closure on May 31,2010)
Time to Loss of Virologic Response at Week 96 (Defined by FDA TLOVR Algorithm - Excluding Study Allowed ARV Substitutions)(NRTI Comparison)
時間枠：Week 96 (using follow-up through to study closure on May 31,2010)
Time from randomization to any of the following events occurring prior to week 96: discontinued ARV regimen (see time to discontinuation of initial ARV therapy above); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values < 400 copies/mL; two consecutive plasma HIV-1 RNA values > 400 copies/mL following virologic suppression.
Week 96 (using follow-up through to study closure on May 31,2010)
Time to Loss of Virologic Response at Week 48 (Defined by FDA TLOVR Algorithm - Including All ARV Substitutions)(NRTI Comparison)
時間枠：Week 48 using follow-up through study closure on May 31,2010
Time from randomization to any of the following events occurring prior to week 48: changed any ARV medication (including permanent discontinuation of all medications); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values < 400 copies/mL; two consecutive plasma HIV-1 RNA values > 400 copies/mL following virologic suppression.
Week 48 using follow-up through study closure on May 31,2010
Time to Loss of Virologic Response at Week 96 (Defined by FDA TLOVR Algorithm - Including All ARV Substitutions)(NRTI Comparison)
時間枠：Week 96 using follow-up through study closure on May 31,2010
Time to any of the following events occurring prior to week 96: changed any ARV medication (including permanent discontinuation of all medications); discontinued study follow-up or died; absence of virologic suppression defined as 2 consecutive plasma HIV-1 RNA values < 400 copies/mL; two consecutive plasma HIV-1 RNA values > 400 copies/mL following virologic suppression.
Week 96 using follow-up through study closure on May 31,2010
Time to First Dose Modification or Grade 3 or 4 Adverse Event (NRTI Comparison)
時間枠：Throughout study follow-up until study closure (May 31, 2010)
Time from treatment dispensation to the first occurring of the following: week of first ARV medication change; week of first grade 3 or higher sign/symptom or laboratory abnormality (total bilirubin was excluded) that was at least one grade higher than baseline. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.
Throughout study follow-up until study closure (May 31, 2010)

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

AIDS Clinical Trials Group

協力者

National Institute of Allergy and Infectious Diseases (NIAID)

捜査官

  • スタディチェア：Thomas B. Campbell, MD、University of Colorado, Denver
  • スタディチェア：Timothy Flanigan, MD、The Miriam Hospital
  • スタディチェア：James Hakim, MscClinEpi, FRCP、Department of Medicine, University of Zimbabwe
  • スタディチェア：Nagalingeswaran Kumarasamy, MD、Centre for AIDS Research and Education

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2005年5月1日

一次修了 (実際)

2010年5月1日

研究の完了 (実際)

2010年5月1日

試験登録日

最初に提出

2004年6月7日

QC基準を満たした最初の提出物

2004年6月7日

最初の投稿 (見積もり)

2004年6月8日

学習記録の更新

投稿された最後の更新 (実際)

2018年10月10日

QC基準を満たした最後の更新が送信されました

2018年9月11日

最終確認日

2018年9月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • ACTG A5175
  • 1U01AI068636 (米国 NIH グラント/契約)
  • 5K24AI051966-03 (米国 NIH グラント/契約)
  • PEARLS
  • A5185s

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

購読する