<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/NCT03259698</url>
  </required_header>
  <id_info>
    <org_study_id>CTN 287</org_study_id>
    <nct_id>NCT03259698</nct_id>
  </id_info>
  <brief_title>Optimizing the Delivery of HIV nPEP</brief_title>
  <official_title>Optimizing the Delivery of HIV Post-exposure Prophylaxis: A Randomized Controlled Trial of Text Messaging Support and Physician to Nurse Task-shifting</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Unity Health Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>CIHR Canadian HIV Trials Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Unity Health Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Despite decades of traditional prevention efforts based on behavior change and condom use,&#xD;
      Ontario has seen over 700 new HIV infections annually over the past 10 years. Post-exposure&#xD;
      prophylaxis (PEP) is one such approach, in which uninfected persons use 28 days of&#xD;
      antiretroviral medications (ARVs) shortly after an HIV exposure to minimize the risk of&#xD;
      acquiring HIV. PEP is highly efficacious, is considered a standard of care intervention based&#xD;
      on medical and ethical grounds, and is supported by treatment guidelines. Yet several&#xD;
      implementation challenges have limited its clinical and public health impact in Ontario,&#xD;
      where no formal PEP policy exists. Our proposal seeks to optimize two aspects of delivering&#xD;
      PEP for sexual exposures (nPEP). Results will inform the development of a standardized&#xD;
      approach to nPEP both province-wide and elsewhere.&#xD;
&#xD;
      Thus study has pragmatic, multicenter randomized controlled trial using a 2x2 factorial&#xD;
      design to determine whether the proportion of nPEP patients that successfully complete&#xD;
      follow-up:&#xD;
&#xD;
        1. is higher among those receiving mobile phone-based text messaging support than among&#xD;
           those receiving standard care; and&#xD;
&#xD;
        2. is non-inferior among those receiving care from a sexual health clinic nurse compared to&#xD;
           those receiving hospital-based physician care.&#xD;
&#xD;
      The prospective, randomized, non-blinded, 2x2 factorial trial that will enroll 318 study&#xD;
      participants in Toronto. In Intervention A, we will randomize half of study participants to a&#xD;
      text messaging support service ('WelTel'), in which a trained, community-based counselor&#xD;
      provides standardized weekly 'check-in' messages during their 12-week course of PEP&#xD;
      follow-up. The other half will receive standard care, which does not include any form of&#xD;
      active outreach or reminders outside of scheduled appointments. In Intervention B, we will&#xD;
      randomize half of participants to receive nurse-led care for PEP follow-up at a local sexual&#xD;
      health clinic; the other half will receive standard care by a hospital-based ID physician.&#xD;
      The specific activities for each follow-up visit will be clearly defined in a medical&#xD;
      directive. In keeping with Ontario legislation on medical directives, nurses will review&#xD;
      cases with their authorizing physician or nurse practitioner on a routine basis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 4, 2021</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Self-reported completion of a full course of PEP medications and receipt of a final HIV test result from their nPEP provider 12 weeks after the index exposure</measure>
    <time_frame>12 weeks</time_frame>
    <description>Determined by patient completion of acceptability questionnaire and evidence of HIV test result</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability of TAF/FTC/ELV/cobi-based nPEP]</measure>
    <time_frame>12 weeks</time_frame>
    <description>Collection of adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Completion of each scheduled follow-up activity (blood tests and clinic visits)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Measured by study visit attendance on CRFs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnosis of incident HIV</measure>
    <time_frame>12 weeks</time_frame>
    <description>Determined through laboratory analysis of blood, urine and mucosal swab samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sexually transmitted infections (gonorrhea, chlamydia, syphilis, hepatitis B and C)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Determined through laboratory analysis of blood sample</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported sexual risk-taking behaviour</measure>
    <time_frame>12 weeks</time_frame>
    <description>The following activities will be captured in a questionnaire: number of unprotected vaginal/anal sex acts, and for men who have sex with men, score on a HIV risk index (based on the validated HIRI-MSM)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numbers and types of linkages made by PEP providers to other forms of healthcare</measure>
    <time_frame>Week 12</time_frame>
    <description>Number of participants referred to psychiatry/mental health services and&#xD;
Number of participants referred to addictions/substance services</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction with their PEP experience</measure>
    <time_frame>12 weeks</time_frame>
    <description>Collected using a patient survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inquiries from participants to the PEP provider outside of scheduled follow-up</measure>
    <time_frame>12 weeks</time_frame>
    <description>the number of times participants contacted their healthcare provider outside of scheduled follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PEP-related referrals for physician consultation</measure>
    <time_frame>12 weeks</time_frame>
    <description>Number of times a participant randomized to the nurse-led arm had to be referred to a physician; captured on the sexual health clinic documentation.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Assessment of cost on heathcare system</measure>
    <time_frame>Week 12</time_frame>
    <description>Prospective collection of cost data during the trial to inform a future health economic analysis from the perspective of the healthcare system.</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">434</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>ARM 1 = TEXT MESSAGING SUPPORT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PEP will be delivered by ID physician and participants will receive weekly text message &quot;check-ins&quot; and optional automated text appointment reminders via the WelTel system.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM 2 = NO TEXT MESSAGING SUPPORT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PEP will be delivered according to the standard of care by an infectious diseases physician. Participants will not receive text message reminders or &quot;check-in&quot;.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM 3 = NURSE-LED nPEP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PEP will be delivered by a sexual health clinic nurse operating under a medical directive.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM 4 = ID PHYSICIAN-LED nPEP,</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>PEP will be delivered according to the standard of care by an infectious diseases physician.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nPEP</intervention_name>
    <description>Participants will receive Bictegravir/emtricitabine/tenofovir alafenamide 50/200/25mg (Biktarvy®) one tablet once daily as study drug to complete a 28 day course of PEP.</description>
    <arm_group_label>ARM 1 = TEXT MESSAGING SUPPORT</arm_group_label>
    <arm_group_label>ARM 2 = NO TEXT MESSAGING SUPPORT</arm_group_label>
    <arm_group_label>ARM 3 = NURSE-LED nPEP</arm_group_label>
    <arm_group_label>ARM 4 = ID PHYSICIAN-LED nPEP,</arm_group_label>
    <other_name>Biktarvy</other_name>
    <other_name>Bictegravir/emtricitabine/tenofovir alafenamide</other_name>
    <other_name>BIC/FTC/TAF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Text Messaging Support</intervention_name>
    <description>Text messaging support service ('WelTel'): community-based counselors will provides standardized weekly 'check-in' messages during the participants 12-week course of nPEP follow-up. Participants in the text-message arm will also have the option of receiving generic non-specific automated text reminders of their upcoming appointments in the form of &quot;Don't forget about tomorrow&quot;.</description>
    <arm_group_label>ARM 1 = TEXT MESSAGING SUPPORT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Nurse-Led nPEP</intervention_name>
    <description>nPEP follow-up is provided by nurse-led care at a local sexual health clinic instead of a hospital-based ID physician.</description>
    <arm_group_label>ARM 3 = NURSE-LED nPEP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be 18 years or older&#xD;
&#xD;
          2. Be known or presumed to be HIV-uninfected at baseline&#xD;
&#xD;
          3. Be initiated on PEP by a healthcare provider in the past six days for a sexual&#xD;
             exposure to a known or suspected HIV-infected source&#xD;
&#xD;
          4. STAGE 1 only: Own a mobile phone with text messaging capabilities on which they are&#xD;
             willing to potentially receive messages from the text messaging service&#xD;
&#xD;
          5. Be capable of communicating verbally and via text in English&#xD;
&#xD;
          6. Be planning to continue their follow-up locally or be willing to have follow-up study&#xD;
             visits conducted remotely; either by telephone or via an encrypted video conferencing&#xD;
             system (such as Zoom for healthcare).&#xD;
&#xD;
          7. Be referred to a sexual assault center and provided with necessary counselling and&#xD;
             support services if presented for nPEP following sexual assault.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Creatinine clearance &lt;30 mL/min (using Cockcroft-Gault formula)&#xD;
&#xD;
          2. Enrolled in any other clinical trial of an HIV prevention intervention&#xD;
&#xD;
          3. Prior participation in this clinical trial for a previous episode of nPEP&#xD;
&#xD;
          4. Known co-infection with chronic hepatitis B at enrollment&#xD;
&#xD;
          5. Current or planned pregnancy or breastfeeding&#xD;
&#xD;
          6. Use of a medication whose co-administration with Biktarvy is contraindicated&#xD;
             (dofetilide, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin,&#xD;
             rifampicin, rifabutin, rifapentine, modafinil, dexamethasone, metformin, St. John's&#xD;
             Wort)&#xD;
&#xD;
          7. Concomitant use of HIV pre-exposure prophylaxis (PrEP)&#xD;
&#xD;
          8. Stage 2 only: Concomitant use of any non-prescription medication, supplement, vitamin&#xD;
             or natural remedy which the patient is unwilling to discontinue during Biktarvy®&#xD;
             administration&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Darrell HS Tan, MD, FRCPC, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Unity Health Toronto</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Isaac I Bogoch, MD, FRCPC, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Toronto General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Darrell HS Tan, MD, FRCPC, PhD</last_name>
    <phone>416-864-5568</phone>
    <email>darrell.tan@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Attia Qamar, BME</last_name>
    <email>Attia.Qamar@UnityHealth.to</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>HIV Prevention Clinic (Toronto General Hospital)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Karla Fisher, BSc, MSc</last_name>
      <email>Karla.Fisher@uhn.ca</email>
    </contact>
    <investigator>
      <last_name>Isaac Bogoch, MD MS FRCPC</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Positive Care Clinic (St. Michael's Hospital)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Attia Qamar, BME</last_name>
      <email>Attia.Qamar@unityhealth.to</email>
    </contact>
    <investigator>
      <last_name>Darrell Tan, MD FRCPC, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Crossways Sexual Health Clinic (TPH)</name>
      <address>
        <city>Toronto</city>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Natalie Fawcett, BSN, MSN, NP</last_name>
      <email>Natalie.Fawcett@toronto.ca</email>
    </contact>
    <investigator>
      <last_name>Allison Chris, MD CCFP FRCPC</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>November 19, 2021</last_update_submitted>
  <last_update_submitted_qc>November 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Emtricitabine</mesh_term>
    <mesh_term>Emtricitabine tenofovir alafenamide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03259698
org study id: CTN 287
nct id: NCT03259698
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Despite decades of traditional prevention efforts based on behavior change and condom use,
      Ontario has seen over 700 new HIV infections annually over the past 10 years. Post-exposure
      prophylaxis (PEP) is one such approach, in which uninfected persons use 28 days of
      antiretroviral medications (ARVs) shortly after an HIV exposure to minimize the risk of
      acquiring HIV. PEP is highly efficacious, is considered a standard of care intervention based
      on medical and ethical grounds, and is supported by treatment guidelines. Yet several
      implementation challenges have limited its clinical and public health impact in Ontario,
      where no formal PEP policy exists. Our proposal seeks to optimize two aspects of delivering
      PEP for sexual exposures (nPEP). Results will inform the development of a standardized
      approach to nPEP both province-wide and elsewhere.

      Thus study has pragmatic, multicenter randomized controlled trial using a 2x2 factorial
      design to determine whether the proportion of nPEP patients that successfully complete
      follow-up:

        1. is higher among those receiving mobile phone-based text messaging support than among
           those receiving standard care; and

        2. is non-inferior among those receiving care from a sexual health clinic nurse compared to
           those receiving hospital-based physician care.

      The prospective, randomized, non-blinded, 2x2 factorial trial that will enroll 318 study
      participants in Toronto. In Intervention A, we will randomize half of study participants to a
      text messaging support service ('WelTel'), in which a trained, community-based counselor
      provides standardized weekly 'check-in' messages during their 12-week course of PEP
      follow-up. The other half will receive standard care, which does not include any form of
      active outreach or reminders outside of scheduled appointments. In Intervention B, we will
      randomize half of participants to receive nurse-led care for PEP follow-up at a local sexual
      health clinic; the other half will receive standard care by a hospital-based ID physician.
      The specific activities for each follow-up visit will be clearly defined in a medical
      directive. In keeping with Ontario legislation on medical directives, nurses will review
      cases with their authorizing physician or nurse practitioner on a routine basis.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Self-reported completion of a full course of PEP medications and receipt of a final HIV test result from their nPEP provider 12 weeks after the index exposure
time frame: 12 weeks
description: Determined by patient completion of acceptability questionnaire and evidence of HIV test result
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability of TAF/FTC/ELV/cobi-based nPEP]
time frame: 12 weeks
description: Collection of adverse events
measure: Completion of each scheduled follow-up activity (blood tests and clinic visits)
time frame: 12 weeks
description: Measured by study visit attendance on CRFs
measure: Diagnosis of incident HIV
time frame: 12 weeks
description: Determined through laboratory analysis of blood, urine and mucosal swab samples
measure: Sexually transmitted infections (gonorrhea, chlamydia, syphilis, hepatitis B and C)
time frame: 12 weeks
description: Determined through laboratory analysis of blood sample
measure: Self-reported sexual risk-taking behaviour
time frame: 12 weeks
description: The following activities will be captured in a questionnaire: number of unprotected vaginal/anal sex acts, and for men who have sex with men, score on a HIV risk index (based on the validated HIRI-MSM)
measure: Numbers and types of linkages made by PEP providers to other forms of healthcare
time frame: Week 12
description: Number of participants referred to psychiatry/mental health services and
Number of participants referred to addictions/substance services
measure: Patient satisfaction with their PEP experience
time frame: 12 weeks
description: Collected using a patient survey
measure: Inquiries from participants to the PEP provider outside of scheduled follow-up
time frame: 12 weeks
description: the number of times participants contacted their healthcare provider outside of scheduled follow-up
measure: PEP-related referrals for physician consultation
time frame: 12 weeks
description: Number of times a participant randomized to the nurse-led arm had to be referred to a physician; captured on the sexual health clinic documentation.
measure: Assessment of cost on heathcare system
time frame: Week 12
description: Prospective collection of cost data during the trial to inform a future health economic analysis from the perspective of the healthcare system.
arm group label: ARM 1 = TEXT MESSAGING SUPPORT
arm group type: Experimental
description: PEP will be delivered by ID physician and participants will receive weekly text message "check-ins" and optional automated text appointment reminders via the WelTel system.
arm group label: ARM 2 = NO TEXT MESSAGING SUPPORT
arm group type: Experimental
description: PEP will be delivered according to the standard of care by an infectious diseases physician. Participants will not receive text message reminders or "check-in".
arm group label: ARM 3 = NURSE-LED nPEP
arm group type: Experimental
description: PEP will be delivered by a sexual health clinic nurse operating under a medical directive.
arm group label: ARM 4 = ID PHYSICIAN-LED nPEP,
arm group type: Active Comparator
description: PEP will be delivered according to the standard of care by an infectious diseases physician.
intervention type: Drug
intervention name: nPEP
description: Participants will receive Bictegravir/emtricitabine/tenofovir alafenamide 50/200/25mg (Biktarvy®) one tablet once daily as study drug to complete a 28 day course of PEP.
arm group label: ARM 1 = TEXT MESSAGING SUPPORT
arm group label: ARM 2 = NO TEXT MESSAGING SUPPORT
arm group label: ARM 3 = NURSE-LED nPEP
arm group label: ARM 4 = ID PHYSICIAN-LED nPEP,
other name: Biktarvy
other name: Bictegravir/emtricitabine/tenofovir alafenamide
other name: BIC/FTC/TAF
intervention type: Behavioral
intervention name: Text Messaging Support
description: Text messaging support service ('WelTel'): community-based counselors will provides standardized weekly 'check-in' messages during the participants 12-week course of nPEP follow-up. Participants in the text-message arm will also have the option of receiving generic non-specific automated text reminders of their upcoming appointments in the form of "Don't forget about tomorrow".
arm group label: ARM 1 = TEXT MESSAGING SUPPORT
intervention type: Other
intervention name: Nurse-Led nPEP
description: nPEP follow-up is provided by nurse-led care at a local sexual health clinic instead of a hospital-based ID physician.
arm group label: ARM 3 = NURSE-LED nPEP
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Darrell HS Tan, MD, FRCPC, PhD
role: Principal Investigator
affiliation: Unity Health Toronto
last name: Isaac I Bogoch, MD, FRCPC, MSc
role: Principal Investigator
affiliation: Toronto General Hospital
last name: Darrell HS Tan, MD, FRCPC, PhD
phone: 416-864-5568
email: darrell.tan@gmail.com
last name: Attia Qamar, BME
email: Attia.Qamar@UnityHealth.to
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Canada
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Tenofovir
mesh term: Emtricitabine
mesh term: Emtricitabine tenofovir alafenamide
sharing ipd: Undecided