Efficacy of Envarsus XR and Digital Health Technology in Reducing Tacrolimus Fluctuation and Frequency of Dose Changes

NCT04711291 | Withdrawn DMC

• 1 other identifier: 2020P001109
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Tacrolimus is an immunosuppressive agent prescribed to prevent organ rejection in post transplant patients, in combination with other immunosuppressants. In post-kidney transplant patients, tacrolimus blood trough(peak) level must be monitored frequently, and dose adjustments must be made as necessary to keep trough level within a very narrow target range. High tacrolimus intra-patient variability(IPV) can be a marker of medication non-adherence. The presence of medication non-adherence could be due to multiple factors e.g. Forgetfulness, misunderstanding or miscommunication due to language barrier etc. Our hypothesis is using QR code technology along with extended release Tacrolimus medication will reduce tacrolimus IPV fluctuation.

Conditions

Medication Adherence; Renal Transplant

Keywords

QR code technology; Envarsus-XR; Tacrolimus trough level; Digital health technology

Outcome Measures

Primary Outcomes (1)

• Number of tacrolimus dose changes in 12 month period.

  How frequent was the dose changes in 12 month follow up post transplant, excluding changes made due to change in therapeutic target.

  1 year follow up

Secondary Outcomes (3)

• Change in number of tacrolimus dose adjustments in follow up period compared to 12 months prior to enrolment, excluding changes made due to change in therapeutic target

  12 months

• Self-reported adherence via monthly questionnaire.

  12 months

• • Variability in tacrolimus trough levels, as checked on routine labs as part of standard care

  12 months

Study Arms (3)

Remain on IR-Tac prescribed doses every 12 hours

NO INTERVENTION

Patient will remain in Tacrolimus IR-Tac Arm and will complete medication adherence questionnaire monthly. They will not receive any notifications from TransMedAx application. Research staff and PI will collect their Tacrolimus Trough levels and change in tacrolimus dose levels during their routine follow up.

Convert to Envarsus XR once daily

ACTIVE COMPARATOR

Subjects randomized to this arm will switch from IR-Tac to Envarsus XR and will complete medication adherence questionnaire. However, patients in this group will not receive any notifications from TransMedAx application. Research staff and PI will collect their Tacrolimus trough levels and change in tacrolimus dose during their follow up.

Drug: Convert to Envarsus XR once daily

Convert to Envarsus XR once daily combined with TransMedAx app use

EXPERIMENTAL

Subjects randomized to this arm will switch from IR-Tac to Envarsus XR, will receive notification by scanning a QR code through TransMedAx application and will complete medication adherence questionnaire. Research staff and PI will collect their Tacrolimus trough levels and change in tacrolimus dose during their follow up.

Combination Product: Conversion to Envarsus-XR and use of smart phone app, TransMedAx

Interventions

Conversion to Envarsus-XR and use of smart phone app, TransMedAx COMBINATION_PRODUCT

Convert to tacrolimus extended release (Envarsus XR) prescribed dose every 24 hours used in combination with the smart phone application, TransMedAx. Patients in this arm will be trained to use the app along with conversion to Envarsus-XR. Once patient scan the code on medicine bottle and the app will remind them about the time and dose of the medication in their native language.

Convert to Envarsus XR once daily combined with TransMedAx app use

Convert to Envarsus XR once daily DRUG

Convert from tacrolimus immediate release to tacrolimus extended release (Envarsus XR) prescribed dose every 24 hours

Convert to Envarsus XR once daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BIDMC adult kidney transplant recipient more than 2 years post transplant
• On tacrolimus IR regimen
• Estimated glomerular filtration rate (eGFR) \>45
• Tacrolimus dose adjustments 2 or more times in past 12 months
• Own and able to use a smart phone.
• Able to consent

You may not qualify if:

• Prisoners
• Patients with primary language other than English, Spanish, Haitian/Creole, Mandarin
• Patients who can't swallow whole tablets or capsules.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Veloxis Pharmaceuticals: collaborator

Related Publications (14)

• Borra LC, Roodnat JI, Kal JA, Mathot RA, Weimar W, van Gelder T. High within-patient variability in the clearance of tacrolimus is a risk factor for poor long-term outcome after kidney transplantation. Nephrol Dial Transplant. 2010 Aug;25(8):2757-63. doi: 10.1093/ndt/gfq096. Epub 2010 Feb 26.

  PMID: 20190242 BACKGROUND

• Kahan BD, Welsh M, Urbauer DL, Mosheim MB, Beusterien KM, Wood MR, Schoenberg LP, Dicesare J, Katz SM, VAN Buren CT. Low intraindividual variability of cyclosporin A exposure reduces chronic rejection incidence and health care costs. J Am Soc Nephrol. 2000 Jun;11(6):1122-1131. doi: 10.1681/ASN.V1161122.

  PMID: 10820177 BACKGROUND

• Sapir-Pichhadze R, Wang Y, Famure O, Li Y, Kim SJ. Time-dependent variability in tacrolimus trough blood levels is a risk factor for late kidney transplant failure. Kidney Int. 2014 Jun;85(6):1404-11. doi: 10.1038/ki.2013.465. Epub 2013 Dec 11.

  PMID: 24336032 BACKGROUND

• Shen CL, Yang AH, Lien TJ, Tarng DC, Yang CY. Tacrolimus Blood Level Fluctuation Predisposes to Coexisting BK Virus Nephropathy and Acute Allograft Rejection. Sci Rep. 2017 May 16;7(1):1986. doi: 10.1038/s41598-017-02140-1.

  PMID: 28512328 BACKGROUND

• Shuker N, Cadogan M, van Gelder T, Roodnat JI, Kho MM, Weimar W, Hesselink DA. Conversion from twice-daily to once-daily tacrolimus does not reduce intrapatient variability in tacrolimus exposure. Ther Drug Monit. 2015 Apr;37(2):262-9. doi: 10.1097/FTD.0000000000000136.

  PMID: 25265255 BACKGROUND

• Rostaing L, Bunnapradist S, Grinyo JM, Ciechanowski K, Denny JE, Silva HT Jr, Budde K; Envarsus Study Group. Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial. Am J Kidney Dis. 2016 Apr;67(4):648-59. doi: 10.1053/j.ajkd.2015.10.024. Epub 2015 Dec 22.

  PMID: 26717860 BACKGROUND

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  PMID: 29602631 BACKGROUND

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  PMID: 25455760 BACKGROUND

• Quintana Y, Fahy D, Crotty B, Jain R, Kaldany E, Gorenberg M, Lipsitz L, Engorn D, Rodriguez J, Orfanos A, Bajracharya A, Henao J, Adra M, Skerry D, Slack WV, Safran C. InfoSAGE: Supporting Elders and Families through Online Family Networks. AMIA Annu Symp Proc. 2018 Dec 5;2018:932-941. eCollection 2018.

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  PMID: 18373144 BACKGROUND

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  PMID: 26113208 BACKGROUND

MeSH Terms

Conditions

Medication Adherence

Condition Hierarchy (Ancestors)

Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Study Officials

• Nikhil Agrawal, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

• Martha Pavlakis, MD

  Beth Israel Deaconess Medical Center

  STUDY DIRECTOR

• Amtul Aala, MD

  Beth Israel Deaconess Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: BIDMC kidney transplant patients currently taking immediate release tacrolimus (IR-Tac) will be screened for enrollment into the trial. Eligible patients will be randomized to one of three treatment arms in a 1:1:1 fashion. We aim to randomize seventy-five (75) patients into one of three treatment arms (1:1:1) as described. Arm 1: Remain on tacrolimus immediate release (IR-Tac) prescribed doses every 12 hours; Arm 2: Convert to tacrolimus extended release (Envarsus XR) prescribed dose every 24 hours; OR Arm 3: Convert to tacrolimus extended release (Envarsus XR) prescribed dose every 24 hours used in combination with the smart phone application, TransMedAxTM.

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 15, 2021
• Study Start: June 1, 2017
• Primary Completion: December 31, 2022
• Study Completion: July 1, 2023
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share