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

Study Overview
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Brief Summary
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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
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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.

Official Title
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CCTG 595: A Multicenter, Randomized Study of Text Messaging to Improve Adherence to PrEP in Risky MSM

Conditions
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Patient Adherence, HIV Seronegativity

Intervention / Treatment
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* Device: SoC + iTab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care (SoC)<br>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<br>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. | Device: SoC + iTab<br>* Text messaging reminders to improve adherence to PrEP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to PrEP | 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. | Baseline to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perfect Adherence to PrEP | 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. | Baseline to Week 48 | 
| Rate of HIV Seroconversion | 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. | Up to 2.5 years after baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PrEP, Pre exposure Prophylaxis, Text Messaging, Truvada, iTab, CCTG, 595