CCTG 595: Text Messaging Intervention to Improve Adherence to PrEP in High-risk MSM

• ClinicalTrials.gov Identifier: NCT01761643
• Recruitment Status: Completed
• First Posted: January 7, 2013
• Results First Posted: June 2, 2020
• Last Update Posted: June 30, 2020
• Sponsor: University of California, San Diego
• Collaborators: University of California, Los Angeles; University of Southern California; City of Long Beach Department of Health and Human Services; California HIV/AIDS Research Program; Gilead Sciences
• Information provided by (Responsible Party): Sheldon Morris, University of California, San Diego

Tracking Information

• First Submitted Date: January 2, 2013
• First Posted Date: January 7, 2013
• Results First Submitted Date: May 13, 2020
• Results First Posted Date: June 2, 2020
• Last Update Posted Date: June 30, 2020
• Actual Study Start Date: December 19, 2012
• Actual Primary Completion Date: June 13, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 13, 2020)

Adherence to PrEP [ Time Frame: Baseline to Week 48 ]

Proportion of participants adherent to PrEP as measured by TFV-DP dried blood spot (DBS) concentrations > 719 fmol/punch at Week 12 and the last on-drug visit.

Original Primary Outcome Measures (submitted: January 3, 2013)

Adherence to PrEP [ Time Frame: Baseline to Week 48 ]

CCTG 595 will compare adherence to fixed dose TDF/FTC, between subjects randomized to receive SoC plus text message reminders versus SoC, when used for pre-exposure prophylaxis among MSM at high risk for HIV acquisition. The primary outcome is defined as a composite endpoint of remaining on PrEP and having adherence > 90% over 48 weeks of follow-up. The adherence endpoint will be derived from the 4 day ACTG adherence assessment from each of the visits from week 4, 12, 24, 36, and 48. 'Adherent' will be defined as self-reported TDF/ FTC adherence of 90% or greater (at least 18 of 20 days). If a subject misses an adherence assessment within the window of a scheduled visit or discontinues study prior to week 48, then the missed visits will be counted no adherence for the time of that visit. All randomized subjects that were dispensed PrEP at baseline will be included in the modified intent-to-treat analysis.

Current Secondary Outcome Measures (submitted: May 13, 2020)

• Perfect Adherence to PrEP [ Time Frame: Baseline to Week 48 ]
  Proportion of participants with perfect adherence to PrEP as measured by TFV-DP dried blood spot (DBS) concentrations > 1246 fmol/punch at Week 12 and the last on-drug visit.
• Rate of HIV Seroconversion [ Time Frame: Up to 2.5 years after baseline ]
  Determine the rate of HIV seroconversion in PrEP users and compare the iTAB to SOC arms for number of new infections as a proportion at 48 weeks and end of study.

Original Secondary Outcome Measures (submitted: January 3, 2013)

• Adherence in subjects that remain on PrEP [ Time Frame: Baseline to Week 48, and up to 2.5 years follow up if subject desires to remain on study after reaching the primary endpoint ]
  Compare adherence to TDF/FTC in the iTAB versus SoC in the subjects that remain on PrEP (at 48 weeks and up to 2.5 years follow up) by the continuous measure of percent days adherent by the cumulative 4 day ACTG and the visual analog scale (VAS) recall in an 'as treated' analysis.
• Adherence to PrEP for duration of study [ Time Frame: Baseline to Week 48, and up to 2.5 years follow up if subject desires to remain on study after reaching the primary endpoint ]
  Compare adherence to TDF/FTC in the iTab versus SoC groups for the duration of the study (up to 2.5 years). Adherence will be compared using the same outcomes as the Primary Outcome Measure (self-reported to be on drug and 90% adherent and 100% detectable FTC at each scheduled visit) as modified intent to treat analysis.
• Factors associated with poor adherence [ Time Frame: Baseline to Week 48 ]
  Determine factors associated with poor adherence/lost to PrEP in study participants (outcomes of < 90% adherent on drug at 48 weeks by ACTG 4 day recall or discontinuation of drug). Factors associated with poor adherence to TDF/FTC will include demographics, ongoing substance use, untreated mental illness, socioeconomic status, low health/HIV and system literacy, fear of disclosure and non-English language.
• Factors associated with discontinuation of TDF/FTC [ Time Frame: Baseline to Week 48 ]
  Determine the factors associated with discontinuation of TDF/FTC at any time point including change in perceived and actual risk of HIV acquisition, demographics, ongoing substance use, untreated mental illness, socioeconomic status, low health/HIV and system literacy, fear of disclosure and non-English language.
• Rate of HIV seroconversion [ Time Frame: Baseline to Week 48, and up to 2.5 years follow up if subject desires to remain on study after reaching the primary endpoint ]
  Determine the rate of HIV seroconversion in PrEP users and compare the iTAB to SOC arms for number of new infections as a proportion at 48 weeks and end of study.
• Acquisition of other sexually transmitted infections [ Time Frame: Baseline to Week 48, and up to 2.5 years follow up if subject desires to remain on study after reaching the primary endpoint ]
  Measure acquisition of other sexually transmitted infections (STIs); the proportion of subjects with any new STI at any site will be compared between the iTAB to SOC arms at 48 weeks and through the end of the study.
• Changes in risk behavior [ Time Frame: Baseline until up to 2.5 years follow up ]
  Evaluate changes in risk behavior after initiation of PrEP (risk compensation) comparing baseline to subsequent visits for number of HIV positive/unknown status partners and any unprotected anal intercourse with an HIV positive/ unknown status partner.
• Safety and tolerability of daily TDF/FTC [ Time Frame: Baseline until up to 2.5 years of follow up ]
  Evaluate the safety and tolerability of daily TDF/FTC given for PrEP including discontinuation for any adverse event, serious adverse events and adverse events (grade 2 or higher).

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: January 3, 2013)

Changes of self-reported adherence [ Time Frame: Baseline until up to 2.5 years of follow up ]

Describe changes over time of self-reported adherence in real time by texting.

Descriptive Information

• Brief Title: CCTG 595: Text Messaging Intervention to Improve Adherence to PrEP in High-risk MSM
• Official Title: CCTG 595: A Multicenter, Randomized Study of Text Messaging to Improve Adherence to PrEP in Risky MSM
• Brief Summary: CCTG 595 is a controlled, open-label, two-arm, randomized (1:1) clinical demonstration project to determine if the use of a text-message based adherence intervention (iTAB) improves retention and adherence to PrEP compared to standard of care (SoC) PrEP delivery.

Detailed Description

A total of 400 HIV-uninfected men who have sex with men (MSM)and male to female (M to F) transgender individuals with recent high-risk transmission behavior will be enrolled into the study. Each subject will be followed for up to 48 weeks after enrollment of the last subject. The primary endpoint will be measured at 48 weeks.

All subjects will start PrEP with TDF + FTC fixed dose combination given once daily. Subjects will be randomized (1:1) to either the iTAB text messaging adherence reminder intervention with SoC or the SoC alone arm. Subjects placed into the iTAB intervention arm will receive a personalized, automated texting system to maintain adherence and retention. Both groups will receive access to PrEP in accordance with standardized comprehensive methods of prescribing, risk reduction counseling, adherence counseling, and clinical assessments that include safety monitoring, as well as HIV and STD screening.

TDF 300 mg + FTC 200 mg fixed dose combination will be given orally once daily starting at the baseline visit (month 0) and continued throughout the study.

• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

The purpose of this study is to evaluate a promising method of reinforcing PrEP adherence using text message. In this study, we will hope to learn if text message reminders increase PrEP adherence.

Masking: None (Open Label)
Masking Description:

Group 1: PrEP daily, HIV/STI screening, adherence and risk behavior counseling, and safety monitoring Group 2: PrEP daily, HIV/STI screening, adherence and risk behavior counseling, and safety monitoring as well as iTAB text adherence reminders

Primary Purpose: Treatment

Condition

• Patient Adherence
• HIV Seronegativity

Intervention

Device: SoC + iTab

Text messaging reminders to improve adherence to PrEP

Study Arms

• No Intervention: Standard of Care (SoC)

  This proposal will perform a study of potential methods to improve adherence and retention by evaluating standard procedures versus the use of the iTAB platform.

  All subjects will receive SoC that will include health education, clinical assessments, laboratory safety monitoring, STI and HIV screening, HIV risk reduction counseling, assessment of psycho-social barriers, adherence counseling, and completion of a computer based survey.

• Active Comparator: SoC + iTab

  Subjects assigned to the iTAB intervention will receive daily dosing reminders that will be sent for the first 6 weeks and then continue with reminders for the duration of the study.

  Subjects will have visits with the study coordinator to introduce the iTAB texting system.

  Once the time is identified, the text reminder system is automated. Patients will confirm medication taking via text responses to the personalized reminders. If a participant does not respond on three consecutive occasions, a high alert message (chosen by the participant) will be sent. If the subject does not respond to this message, the study coordinator would initiate phone calls to contact the subject and explore barriers.

  Intervention: Device: SoC + iTab

Publications *

• Palmer MJ, Henschke N, Villanueva G, Maayan N, Bergman H, Glenton C, Lewin S, Fonhus MS, Tamrat T, Mehl GL, Free C. Targeted client communication via mobile devices for improving sexual and reproductive health. Cochrane Database Syst Rev. 2020 Jul 14;8(8):CD013680. doi: 10.1002/14651858.CD013680.
• Pasipanodya EC, Jain S, Sun X, Blumenthal J, Ellorin E, Corado K, Dube MP, Daar ES, Morris SR, Moore DJ; California Collaborative Treatment Group (CCTG) TAPIR Study Team. Trajectories and Predictors of Longitudinal Preexposure Prophylaxis Adherence Among Men Who Have Sex With Men. J Infect Dis. 2018 Oct 5;218(10):1551-1559. doi: 10.1093/infdis/jiy368.
• Moore DJ, Jain S, Dube MP, Daar ES, Sun X, Young J, Corado K, Ellorin E, Milam J, Collins D, Blumenthal J, Best BM, Anderson P, Haubrich R, Morris SR. Randomized Controlled Trial of Daily Text Messages to Support Adherence to Preexposure Prophylaxis in Individuals at Risk for Human Immunodeficiency Virus: The TAPIR Study. Clin Infect Dis. 2018 May 2;66(10):1566-1572. doi: 10.1093/cid/cix1055.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 24, 2017): 398
• Original Estimated Enrollment (submitted: January 3, 2013): 400
• Actual Study Completion Date: July 11, 2018
• Actual Primary Completion Date: June 13, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Man or transgender M to F who has sex with men.
• Age 18 years or older.

• Subjects must have substantial ongoing risk of acquisition of HIV as evident by one or more of the following:

  • Has at least one HIV infected sexual partner for ≥4 weeks.
  • No condom use during anal intercourse with ≥3 male sex partners who are HIV-positive or of unknown HIV status during the last 3 months.
  • No condom use during anal sex with ≥1 male partner and STI diagnosis during the last 3 months.
• Negative for HIV infection by rapid HIV test and confirmed negative by NAT or other sensitive method such as antibody- antigen test.

• Acceptable laboratory values in the past 30 days:

  • Calculated creatinine clearance of at least 60 mL/min by the Cockcroft-Gault formula (eCcr (male) in mL/min = [(140 - age in years) x (lean body weight in kg)] / (72 x serum creatinine in mg/dL)
  • Alanine aminotransferase (ALT) and/ or aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN)
  • Hemoglobin > 9 g/dL
  • Absolute neutrophil count > 750/ mm3
  • Platelets > 75,000/ mm3

Exclusion Criteria:

• Unable to give informed consent.
• Active hepatitis B (positive hepatitis B surface antigen (HBSAg) or HBSAg negative/ HB core antibody positive/ HBV PCR positive).

• Has substantial medical condition, that in the opinion of the investigator would preclude participation, as defined by

  • cardiovascular condition that may lead to an increased risk of complication if placed on study drugs.
  • gastrointestinal condition that would impair absorption of study drugs.
  • neurological or psychiatric condition that would significantly impair the ability to adhere to PrEP.
  • calculated GFR < 60 mL/min.
  • alcohol or drug abuse or dependence that would significantly impair the ability to adhere to PrEP (only for those with severe impairment).
  • other medical condition that would unacceptably increase the risk of harm from study drug or significantly impair the ability to adhere to PrEP.
• Suspected sensitivity or allergy to the study drug or any of its components.

• Currently using an essential product or medication that interacts with the study drug such as the following:

  • ART (including nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents)

  • Agents with known nephrotoxic potential:

    • aminoglycoside antibiotics (including gentamicin)
    • IV amphotericin B
    • cidofovir
    • cisplatin
    • foscarnet
    • IV pentamidine
    • IV vancomycin
    • oral or IV gancyclovir
    • other agents with significant nephrotoxic potential

  • Drugs that slow renal excretion

    • Probenecid

  • Immune system modulators

    • Systemic chemotherapeutic agents (i.e. cancer treatment medications)
    • Ongoing systemic corticosteroids (with the exception of short courses of tapering steroid doses for asthma or other self- limited condition).
    • Interleukin-2 (IL-2)
    • Interferon (alpha, beta, or gamma)
  • Other agent known to have a significant interaction with TDF or FTC
  • Proteinuria 2+ or greater by urine dipstick
  • Signs or symptoms suggestive of acute HIV infection
  • Any other reason or condition that in the opinion of the investigator would interfere with participation, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01761643
• Other Study ID Numbers: CCTG 595
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sheldon Morris, University of California, San Diego
• Original Responsible Party: University of California, San Diego
• Current Study Sponsor: University of California, San Diego
• Original Study Sponsor: Same as current

Collaborators

• University of California, Los Angeles
• University of Southern California
• City of Long Beach Department of Health and Human Services
• California HIV/AIDS Research Program
• Gilead Sciences

Investigators

• Principal Investigator: Sheldon Morris, MD, MPH; CCTG, UCSD AVRC
• Study Chair: David Moore, PhD; CCTG, UCSD HNRP

• PRS Account: University of California, San Diego
• Verification Date: June 2020