Trial document





This trial has been registered retrospectively.
drksid header

  DRKS00006321

Trial Description

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Title

PROPHET: Prospective clinical and pharmacoeconomic outcomes study of different first-line antiretroviral treatment strategies

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Trial Acronym

PROPHET-Study

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URL of the Trial

https://prophetstudie.de/zentrum/Seiten/index.aspx

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Brief Summary in Lay Language

The German-Austrian Guidelines for the management of HIV-infection list a number of possible antiretroviral therapy combinations for initial treatment. These are comparable with respect to efficacy. Treatment regimens differ in side effect profiles and cost. To date there are no studies comparing initial treatment regimens used in routine care with respect to clinical efficacy and cost in Germany. The “PROPHET” study deliberately gives no recommendations on regimen use. Important factors being investigated include therapy outcomes, physical and mental well-being, as well as quality of life and health care costs. Objective of this study is to obtain insight into HIV treatment strategies in Germany, in order to identify ways to improve medical care of the HIV-infected population.
480 HIV-infected persons beginning initial anitretroviral therapy will be followed for two years. Clinical and health economic data will be documented and analyzed.

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Brief Summary in Scientific Language

The use of highly active anitretroviral therapy (HAART) led to a significant improvement in mortality in HIV-infected patients. The cohort collaboration ART-CC documented an increase in life expectancy of a 20 year-old HIV-infected patient from 36.1 years in 1996-1999 to 49.4 years in 2003-2005 (ART-CC 2008). Numerous analysis in various regions have recently found that due to the availability of HAART, the life expectancy of HIV-positive persons are approachiing that of the general population (Obel 2011, Hogg 2012, Nakagawa 2012). Despite these improvements, it is important to remember that the ultimate theoretical goal of healing the infection is not attainable at this point-in-time. This means that antiretrovial therapy is life-long and may span decades. Life-long therapy poses a challenge not only for patient adherence, but also for long-term side effect management and psychlogical aspects. Currently a number of antiretroviral regimens may be used for initial treatment with comparable efficacy. Preferred are initial combinations consisting of a backbone of two nucleoside/nucleotide analogs and a non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an integrase inihibitor (eg. German-Austrian Guidelines for antiretroviral therapy of HIV-infection, http://www.daignet.de/site-content/hiv-therapie/leitlinien-1). With the recent approval of two integrase inhbitors Elvitegravir (2013; approved in combination with the backbone TDF+FTC) and Dolutegravir (2014) more therapeutic options have become available for the initial therapy of HIV infection. Most of these combinations have been found to be equipotent from a virological stand-point in randomized, some double-blind, controlled studies. Differences lie in pill burden, side effect profiles, dosing, drug interaction potential, resistance profiles and cost. When selecting an initial regimen, physicians have to consider numerous patient-specific factors, including co-morbidities and the presence of any resistance mutations. Any concurrent medication(s) with potential for drug interactions as well as patient preferences also play an important role. To date there are no studies in Germany investigating the clinical and pharmacoeconic aspects of recommended first-line antiretroviral therapies. Studies, which focused on their efficacy were performed mostly within the setting of phase 3 clinical trials, which does not reflect routine clinical care. In such studies, numerous exclusion criteria are defined, eg. "late presenters" with AIDS-defining illness(es) and low CD4 cell counts prior to therapy begin. These patients still make up a significant proportion of newly diagnosed persons in Germany (Zoufaly 2012). We hence expect an underrepresentation in the current evidence of late presenters and other "problem" patients, such as those co-infected with hepatits B or C, those with many co-morbidities, those with addiction issues or geriatric patients. Additionally, most of these studies are conducted internationally and may not adequately represent the German setting.
Aside from the clinical aspects, this PROPHET study also compares the pharacoeconomic impact between standard recommended initial therapies. There will be no guidelines or preferences communicated as to which regimen be used in order to get insight into routine clinical care.
Also of interest are the reasons for chosing and changing specific regimens.

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Organizational Data

  •   DRKS00006321
  •   2016/02/23
  •   [---]*
  •   yes
  •   Approved
  •   14-5847-BO, Ethik-Kommission der Medizinischen Fakultät der Universität Duisburg-Essen
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   B24 -  Unspecified human immunodeficiency virus [HIV] disease
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Interventions/Observational Groups

  •   Tenofovir (TDF) + Emtricitabin (FTC)
    or
    Abacavir (ABC) + Lamivudin (3TC)
    plus one Not Nucleosidale Reverse Transkriptase Inhibitor (NNRTI) (Efavirenz (EFV) or Nevirapine (NVP) or Rilpivirin (RPV))
  •   Tenofovir (TDF) + Emtricitabin (FTC)
    or
    Abacavir (ABC) + Lamivudin (3TC)
    plus one boosted protease Inhibitor (PI/r) (Darunavir/r (DRV/r) or Lopinavir/r (LPV/r) or Atazanavir/r (ATV/r) or Fosamprenavir/r (FPV/r))
  •   Tenofovir (TDF) + Emtricitabin (FTC)
    or
    Abacavir (ABC) + Lamivudin (3TC)
    plus one Integrase Inhibitor (INI) (Raltegravir (RAL) or Elvitegravir/c (EVG/c) or Dolutegravir (DTG))
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Other
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Health economics
  •   Parallel
  •   N/A
  •   No
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Primary Outcome

The primary endpoints are:
1. Percent of patients with HIV-1 RNA <200 cp/mL at month 24 (ITT analysis)
2. Percent of patients with virological failure. Failure will be defined as confirmed VL>200 cp/mL (based on the DHHS definition of virological failure) or a viral rebound to >200 cp/mL combined with subsequent treatment modification.
3. CD4 cell change from baseline and absolute CD4 cell count at months 12 and 24 (involving ITT and AT analyses), particularly in late presenters (defined as per the European consensus CD4<350/µl and/or history of an AIDS-defining event) in comparison to patients with CD4 ≥350/µl and early/less advanced HIV-disease
4. Percent of late presenters with immune reconstitution to >750 CD4/µl compared to patients with CD4 ≥350/µl and no history of AIDS-defining event
5. Costs and cost effectiveness of current first-line HIV-treatment strategies and HIV-care considering the covariables and methods of the DAGNAE K3A study

Annotations:
Efficacy analyses will be stratified according to: A) The use of the third antiretroviral agent (PI/r versus NNRTI versus INI)
B) NRTI Backbone
C) Baseline HIV-RNA categories (i.e. >100.000 cp/mL vs. <= 100.000 cp/ml) and
D) Baseline CD4 categories (i.e. <200, 200-349, 350-499, ≥500/µl).
For certain questions patients are splitted in late presenters (defined as per the European consensus CD4<350/µl and/or history of an AIDS-defining event) in comparison to patients with CD4 ≥350/µl and early/less advanced HIV-disease.

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Secondary Outcome

The secondary endpoints are:
1. Percent with HIV-1 RNA <200 cp/mL at months 12 (ITT analysis) and 24 (As-treated (AT) analysis)
2. Percent <50 cp/mL at months 12 and 24 (involving ITT analysis (based on the above mentioned snapshot algorithm) and AT analysis)
3. Durability of first-line ART, treatment discontinuations and modifications
4. Clinical outcomes and cost of late presenters (defined as per the European consensus CD4<350 and/or history of an AIDS-defining event) in comparison to patients with early/less advanced HIV-disease
5. Weight, blood pressure, waist/hip-measurement, quality of life, depression and phyisical well-being at baseline, months 12 and 24

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Doctor's Practice 
  • Doctor's Practice 
  • other 
  • other 
  • other 
  • other 
  • University Medical Center 
  • other 
  • University Medical Center 
  • Doctor's Practice 
  • University Medical Center 
  • University Medical Center 
  • other 
  • other 
  • Doctor's Practice 
  • other 
  • University Medical Center 
  • Doctor's Practice 
  • University Medical Center 
  • other 
  • other 
  • Doctor's Practice 
  • Doctor's Practice 
  • Doctor's Practice 
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Recruitment

  •   Actual
  •   2014/08/01
  •   480
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. The patient´s age at the date of inclusion is >18 years
2. Chronic HIV-infection, to date without HIV-treatment and indication of therapy start
3. Signed patient informed consent
4. Planned treatment initiation with backbone consiting of TDF+FTC or ABC+3TC in combination with a third antiretroviral drug
5. The third substance is either a Non-nucleosidale-Reverse-Transcriptase-Inhibitor NNRTI: (Efavirenz, Nevirapin, Rilpivirin), a boosted Protease-Inhibitor (PI/r: Darunavir/r, Lopinavir/r, Atazanavir/r, Fosamprenavir/r) or Integrase-Inhibitor (INI: Raltegravir, Elvitegravir/c, Dolutegravir).

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Exclusion Criteria

1. Initiation of antiretroviral therapy which is not based on a backbone of TDF+FTC or ABC/3TC in combination with a NNRTI, PI/r or INI.
2. Acute HIV-infection, seroconversion
3. Prior use of antiretroviral drugs (a short-term therapy within the scope of a "mother-to-child-transmission-prophylaxis" is allowed)

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Addresses

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    • DAGNÄ e.V. (Deutsche Arbeitsgemeinschaft niedergelassener Ärzte in der Versorgung HIV-Infizierter e.V.) vertreten durch Dr. med. Knud Schewe und Dr. med. Stefan Klauke
    • Perlebergerstr. 27
    • 10559  Berlin
    • Germany
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    • Lehrstuhl für Medizinmanagement Universität Duisburg-Essen, Campus Essen Fachbereich Wirtschaftswissenschaften
    • Mr.  Prof. Dr.  Jürgen  Wasem 
    • Schützenbahn 70
    • 45127  Essen
    • Germany
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    • ICH Study Center
    • Mr.  PD. Dr. med.  Christian  Hoffmann 
    • Grindelallee 35
    • 20146  Hamburg
    • Germany
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    • ICH Study Center
    • Mr.  PD. Dr. med.  Christian  Hoffmann 
    • Grindelallee 35
    • 20146  Hamburg
    • Germany
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Sources of Monetary or Material Support

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    • Janssen-Cilag GmbH
    • Johnson & Johnson Platz 1
    • 41470  Neuss
    • Germany
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    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
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Status

  •   Recruiting complete, follow-up complete
  •   2017/11/14
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Trial Publications, Results and other Documents

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