<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01697046</url>
  </required_header>
  <id_info>
    <org_study_id>IIS# 39550</org_study_id>
    <nct_id>NCT01697046</nct_id>
  </id_info>
  <brief_title>A Pilot Study on Raltegravir, Tenofovir and Emtricitabine for Peri-exposure Prophylaxis for HIV Infection</brief_title>
  <acronym>PERIEP</acronym>
  <official_title>A Pilot Study of the Safety, Acceptability, Behavior Impact, and HIV Seroincidence Among High Risk Men Who Have Sex With Men With Access to Isentress 400 mg BID + Truvada Once Daily for Peri-exposure Chemoprophylaxis for HIV Infection Chemoprophylaxis for HIV Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Projeto Praça Onze</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Projeto Praça Onze</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a pilot, open label study involving 65 participants. All participants will be&#xD;
      followed until seroconversion or until the last enrolled participant completes one year of&#xD;
      follow-up, whichever happens first. Participant study number will be given at the screening&#xD;
      visit, prior to inclusion in the study.&#xD;
&#xD;
      The chosen intervention and study regimen are based on the dynamics of viral infection and&#xD;
      the pharmacokinetics of the study drugs. In order to inhibit reverse transcription nucleoside&#xD;
      and nucleotide analogues need to be phosphorylated intracellularly. On the other hand,&#xD;
      available data indicate that it takes approximately 10 hours between exposure and HIV viral&#xD;
      integration, offering a window of opportunity for Raltegravir to block integration and thus&#xD;
      prevent infection, given that this drug does not need to be metabolized to exert its effect.&#xD;
      The intervention will be maintained for 4 weeks following exposure, in accordance with&#xD;
      Brazilian and CDC guidelines for PEP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects with reported high-risk behavior (and anticipated future high-risk behavior) but no&#xD;
      exposure in the immediate past will be the focus of this study.&#xD;
&#xD;
      Participants will be prescribed raltegravir 400 mg BID + Truvada once daily. All study&#xD;
      participants will receive a 4-days starter pack. Study participants will be instructed to&#xD;
      start study drugs if they expect or experience an exposure of any mucous membrane (oral,&#xD;
      urethral, anal) to semen. Subjects who expect or experience these exposures will be&#xD;
      instructed to take 1 pill of Raltegravir 400mg and one pill of truvada, followed by a second&#xD;
      dose of Raltegravir 12 hours later. From the second day onward, participants will be&#xD;
      instructed to take Raltegravir 400 mg BID + Truvada once daily. The first dose should be&#xD;
      taken no more than 6 hours before or 6 hours after the expected or actual exposure and&#xD;
      continued for 28 days.&#xD;
&#xD;
      Enrolled subjects will also be instructed to report to the study site within 4 days of&#xD;
      beginning study drugs to respond to a CASI questionnaire and to have blood taken. They will&#xD;
      be instructed to return at the end of the 4-week chemoprophylaxis course for reevaluation and&#xD;
      to be given another 4-day supply of medication. Under no circumstances will any participant&#xD;
      be given a greater than 4 week supply of medication; all will be evaluated for toxicity and&#xD;
      adherence following each course of chemoprophylaxis.&#xD;
&#xD;
      The study participants will be monitored closely for safety after each course of&#xD;
      chemoprophylaxis and at the end of the trial. In addition, subjects will be instructed to&#xD;
      immediately contact the site if they experience certain symptoms consistent with severe&#xD;
      toxicity. At each evaluation a careful clinical history, physical examination, and laboratory&#xD;
      assessment, including HIV serology, will be completed. Adherence will be estimated based on&#xD;
      self-report and the use of pill counts. During each visit, subjects will be reminded of the&#xD;
      need to not increase high-risk sexual behavior. HIV serology and response to a CASI&#xD;
      questionnaire will be conducted monthly.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>November 2012</start_date>
  <completion_date type="Anticipated">March 2014</completion_date>
  <primary_completion_date type="Anticipated">March 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety</measure>
    <time_frame>16 months</time_frame>
    <description>Number and severity of adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HIV seroincidence</measure>
    <time_frame>16 months</time_frame>
    <description>Rate of incidence of new infections</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">65</enrollment>
  <condition>Infection</condition>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Isentress+Truvada</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will receive the intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Truvada and Isentress</intervention_name>
    <description>Subjects with reported high-risk behavior (and anticipated future high-risk behavior) but no exposure in the immediate past will be the focus of this study.&#xD;
Participants will be prescribed raltegravir 400 mg BID + Truvada once daily. All study participants will receive a 4-days starter pack. Study participants will be instructed to start study drugs if they expect or experience an exposure of any mucous membrane (oral, urethral, anal) to semen. Subjects who expect or experience these exposures will be instructed to take 1 pill of Raltegravir 400mg and one pill of truvada, followed by a second dose of Raltegravir 12 hours later. From the second day onward, participants will be instructed to take Raltegravir 400 mg BID + Truvada once daily. The first dose should be taken no more than 6 hours before or 6 hours after the expected or actual exposure and continued for 28 days.</description>
    <arm_group_label>Isentress+Truvada</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Individuals will be included in the clinical trial if they meet ALL of the following&#xD;
        criteria:&#xD;
&#xD;
          -  Male sex (at birth);&#xD;
&#xD;
          -  Willing and able to provide written informed consent;&#xD;
&#xD;
          -  Age 18 years or older;&#xD;
&#xD;
          -  HIV-1-uninfected;&#xD;
&#xD;
          -  Absence of signs or symptoms compatible with an acute viral disease&#xD;
&#xD;
          -  Evidence of high risk for acquiring HIV-1 infection including any one of the&#xD;
             following: 1) No condom use during the last receptive and/or insertive anal&#xD;
             intercourse with a male HIV-positive partner or a male partner of unknown HIV status&#xD;
             during the last 6 months; (2) anal intercourse with more than 4 male sex partners&#xD;
             during the last 6 months; (3) exchange of money, gifts, shelter, or drugs for anal sex&#xD;
             with a male partner during the last 6 months; (4) sex with a male partner and STI&#xD;
             diagnosis during the last 6 months or at screening, or (5) sexual partner of an&#xD;
             HIV-infected man with whom condoms are not consistently used.&#xD;
&#xD;
          -  Adequate renal function&#xD;
&#xD;
          -  Adequate hepatic function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Glycosuria or proteinuria&#xD;
&#xD;
          -  Acute hepatitis B infection&#xD;
&#xD;
          -  History of pathological bone fractures not related to trauma&#xD;
&#xD;
          -  Active alcohol or drug use considered sufficient to hinder compliance with any study&#xD;
             procedures&#xD;
&#xD;
          -  At enrollment, has any other condition that, based on the opinion of the investigator&#xD;
             or designee, would preclude provision of informed consent; make participation in the&#xD;
             study unsafe; complicate interpretation of study outcome data; or otherwise interfere&#xD;
             with achieving the study objectives&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mauro Schechter, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Projeto Praça Onze</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Monica Barbosa de Souza, BA</last_name>
    <phone>+55 21 22739073</phone>
    <phone_ext>14</phone_ext>
    <email>monica@ponze.ufrj.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Carina Beppu Yoshida, RN</last_name>
    <phone>+55 21 22739073</phone>
    <phone_ext>15</phone_ext>
    <email>carina@ponze.ufrj.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Monica Barbosa de Souza</name>
      <address>
        <city>Rio de Janeiro</city>
        <state>RJ</state>
        <zip>20210-030</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <contact>
      <last_name>Carina Beppu Yoshida, RN</last_name>
      <phone>+55 21 22739073</phone>
      <phone_ext>15</phone_ext>
      <email>carina@ponze.ufrj.br</email>
    </contact>
    <investigator>
      <last_name>Rafael Quaresma Garrido, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Centers for Disease Control and Prevention (CDC). Update: provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR Morb Mortal Wkly Rep. 1996 Jun 7;45(22):468-80.</citation>
    <PMID>8622618</PMID>
  </reference>
  <reference>
    <citation>Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, Heptonstall J, Ippolito G, Lot F, McKibben PS, Bell DM. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997 Nov 20;337(21):1485-90. doi: 10.1056/NEJM199711203372101.</citation>
    <PMID>9366579</PMID>
  </reference>
  <reference>
    <citation>Schechter M, do Lago RF, Mendelsohn AB, Moreira RI, Moulton LH, Harrison LH; Praca Onze Study Team. Behavioral impact, acceptability, and HIV incidence among homosexual men with access to postexposure chemoprophylaxis for HIV. J Acquir Immune Defic Syndr. 2004 Apr 15;35(5):519-25. doi: 10.1097/00126334-200404150-00010.</citation>
    <PMID>15021317</PMID>
  </reference>
  <reference>
    <citation>Grant, RM; Lama, JR; Anderson, PL; McMahan, V; Liu, AY; Vargas, L; Goicochea, P; Casapía, M; Guanira-Carranza, JV; Ramirez-Cardich, ME; Montoya-Herrera,O; Fernandez, T; Veloso, VG; Buchbinder, SP; Chariyalertsak, S; Schechter, M; Gail -Bekker, L; Mayer, KM; Kallas, EG; Amico, KR; Mulligan, K; Bushman, LR; Hance, TJ; Ganoza, C; Defechereux, P; Brian, P; Wang, F; McConnell, JJ; Zheng, JH; Lee, J; Rooney, JF; Jaffe, HS; Martinez, AI; Burns, DN; Glidden, DV. Pre-Exposure Chemoprophylaxis for HIV Prevention in Men who Have Sex with Men. New Eng J Med 2010; 363:2587-99.</citation>
  </reference>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 24, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <last_update_submitted>September 26, 2012</last_update_submitted>
  <last_update_submitted_qc>September 26, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 2, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Projeto Praça Onze</investigator_affiliation>
    <investigator_full_name>Mauro Schechter</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>peri-exposure</keyword>
  <keyword>chemoprophylaxis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination</mesh_term>
    <mesh_term>Raltegravir Potassium</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01697046
org study id: IIS# 39550
nct id: NCT01697046
lead sponsor: 
collaborator: 
has dmc: No
This will be a pilot, open label study involving 65 participants. All participants will be
      followed until seroconversion or until the last enrolled participant completes one year of
      follow-up, whichever happens first. Participant study number will be given at the screening
      visit, prior to inclusion in the study.

      The chosen intervention and study regimen are based on the dynamics of viral infection and
      the pharmacokinetics of the study drugs. In order to inhibit reverse transcription nucleoside
      and nucleotide analogues need to be phosphorylated intracellularly. On the other hand,
      available data indicate that it takes approximately 10 hours between exposure and HIV viral
      integration, offering a window of opportunity for Raltegravir to block integration and thus
      prevent infection, given that this drug does not need to be metabolized to exert its effect.
      The intervention will be maintained for 4 weeks following exposure, in accordance with
      Brazilian and CDC guidelines for PEP.
Subjects with reported high-risk behavior (and anticipated future high-risk behavior) but no
      exposure in the immediate past will be the focus of this study.

      Participants will be prescribed raltegravir 400 mg BID + Truvada once daily. All study
      participants will receive a 4-days starter pack. Study participants will be instructed to
      start study drugs if they expect or experience an exposure of any mucous membrane (oral,
      urethral, anal) to semen. Subjects who expect or experience these exposures will be
      instructed to take 1 pill of Raltegravir 400mg and one pill of truvada, followed by a second
      dose of Raltegravir 12 hours later. From the second day onward, participants will be
      instructed to take Raltegravir 400 mg BID + Truvada once daily. The first dose should be
      taken no more than 6 hours before or 6 hours after the expected or actual exposure and
      continued for 28 days.

      Enrolled subjects will also be instructed to report to the study site within 4 days of
      beginning study drugs to respond to a CASI questionnaire and to have blood taken. They will
      be instructed to return at the end of the 4-week chemoprophylaxis course for reevaluation and
      to be given another 4-day supply of medication. Under no circumstances will any participant
      be given a greater than 4 week supply of medication; all will be evaluated for toxicity and
      adherence following each course of chemoprophylaxis.

      The study participants will be monitored closely for safety after each course of
      chemoprophylaxis and at the end of the trial. In addition, subjects will be instructed to
      immediately contact the site if they experience certain symptoms consistent with severe
      toxicity. At each evaluation a careful clinical history, physical examination, and laboratory
      assessment, including HIV serology, will be completed. Adherence will be estimated based on
      self-report and the use of pill counts. During each visit, subjects will be reminded of the
      need to not increase high-risk sexual behavior. HIV serology and response to a CASI
      questionnaire will be conducted monthly.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Safety
time frame: 16 months
description: Number and severity of adverse events
measure: HIV seroincidence
time frame: 16 months
description: Rate of incidence of new infections
arm group label: Isentress+Truvada
arm group type: Experimental
description: All participants will receive the intervention
intervention type: Drug
intervention name: Truvada and Isentress
description: Subjects with reported high-risk behavior (and anticipated future high-risk behavior) but no exposure in the immediate past will be the focus of this study.
Participants will be prescribed raltegravir 400 mg BID + Truvada once daily. All study participants will receive a 4-days starter pack. Study participants will be instructed to start study drugs if they expect or experience an exposure of any mucous membrane (oral, urethral, anal) to semen. Subjects who expect or experience these exposures will be instructed to take 1 pill of Raltegravir 400mg and one pill of truvada, followed by a second dose of Raltegravir 12 hours later. From the second day onward, participants will be instructed to take Raltegravir 400 mg BID + Truvada once daily. The first dose should be taken no more than 6 hours before or 6 hours after the expected or actual exposure and continued for 28 days.
arm group label: Isentress+Truvada
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Mauro Schechter, MD, PhD
role: Principal Investigator
affiliation: Projeto Praça Onze
last name: Monica Barbosa de Souza, BA
phone: +55 21 22739073
phone ext: 14
email: monica@ponze.ufrj.br
last name: Carina Beppu Yoshida, RN
phone: +55 21 22739073
phone ext: 15
email: carina@ponze.ufrj.br
facility: 
contact: 
investigator: 
country: Brazil
citation: Centers for Disease Control and Prevention (CDC). Update: provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR Morb Mortal Wkly Rep. 1996 Jun 7;45(22):468-80.
PMID: 8622618
citation: Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, Heptonstall J, Ippolito G, Lot F, McKibben PS, Bell DM. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997 Nov 20;337(21):1485-90. doi: 10.1056/NEJM199711203372101.
PMID: 9366579
citation: Schechter M, do Lago RF, Mendelsohn AB, Moreira RI, Moulton LH, Harrison LH; Praca Onze Study Team. Behavioral impact, acceptability, and HIV incidence among homosexual men with access to postexposure chemoprophylaxis for HIV. J Acquir Immune Defic Syndr. 2004 Apr 15;35(5):519-25. doi: 10.1097/00126334-200404150-00010.
PMID: 15021317
citation: Grant, RM; Lama, JR; Anderson, PL; McMahan, V; Liu, AY; Vargas, L; Goicochea, P; Casapía, M; Guanira-Carranza, JV; Ramirez-Cardich, ME; Montoya-Herrera,O; Fernandez, T; Veloso, VG; Buchbinder, SP; Chariyalertsak, S; Schechter, M; Gail -Bekker, L; Mayer, KM; Kallas, EG; Amico, KR; Mulligan, K; Bushman, LR; Hance, TJ; Ganoza, C; Defechereux, P; Brian, P; Wang, F; McConnell, JJ; Zheng, JH; Lee, J; Rooney, JF; Jaffe, HS; Martinez, AI; Burns, DN; Glidden, DV. Pre-Exposure Chemoprophylaxis for HIV Prevention in Men who Have Sex with Men. New Eng J Med 2010; 363:2587-99.
responsible party type: Principal Investigator
investigator affiliation: Projeto Praça Onze
investigator full name: Mauro Schechter
investigator title: MD, PhD
mesh term: Infections
mesh term: Communicable Diseases
mesh term: HIV Infections
mesh term: Acquired Immunodeficiency Syndrome
mesh term: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
mesh term: Raltegravir Potassium