Kidney Transplant
Conditions
Keywords
Tacrolimus, Mycophenolate, Therapeutic Drug Monitoring
Brief summary
This is a randomized clinical trial to assess an intervention to facilitate patient self-collection of dried blood samples at home for therapeutic drug monitoring of tacrolimus and mycophenolate in kidney transplant recipients. In this study, text messages will be sent to mobile devices to remind kidney transplant recipients to perform therapeutic drug monitoring at home using a special lancet device to collect blood samples from the upper arm. The primary objective is to evaluate if more intensive, bidirectional text messages improve the quality of sample collection.
Detailed description
Optimal immunosuppression therapy, most commonly with tacrolimus and mycophenolate, is critical for kidney transplantation success. While graft and patient survival are multifaceted phenomena, they are commonly attributed to chronic, subclinical immune-mediated damage, tacrolimus nephrotoxicity, or premature death secondary to complications amplified by immunosuppression such as infection, malignancy, and cardiovascular disease. New approaches are required to explore ways to optimize the precision dosing of immunosuppression to reduce the associated significant long-term side effects with the potential to improve kidney transplantation outcomes. Currently, immunosuppressant dose adjustments empirically balance efficacy and toxicity in conjunction with limited tacrolimus blood concentrations. However, both tacrolimus and mycophenolate possess interpatient variability in drug exposure and response with considerable overlap between therapeutic and adverse effects. Only tacrolimus is routinely monitored as mycophenolate trough concentration is not correlated with drug exposure or outcomes. The pharmacokinetic parameter area under the concentration-time curve (AUC) offers a greater understanding of total drug exposure and has been associated with improved outcomes for both tacrolimus and mycophenolate. Yet, AUC is not routinely determined because it is impractical due to the need for multiple repeated samples in the clinic. The investigators propose a prospective, single-center pilot study to evaluate the ability of a text messaging intervention coupled with a novel lancet device, the Tasso-M20, to facilitate the collection of dried blood samples by the patient at home for AUC estimation. The goal of the project is to develop a patient-centric strategy to allow frequent, longitudinal, minimally invasive sample collection which allows for more detailed assessments of immunosuppression exposure. The primary objective is to compare the effect of bidirectional text communication on adherence to and accuracy of home-based AUC collection versus unidirectional text reminders in kidney transplant recipients receiving tacrolimus and mycophenolate. The secondary objective is to assess the bioanalytical agreement of two sample collection methods (dried blood spot and venipuncture) as measured by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS).
Interventions
BEHAVIORALAutomated text messages
Automated text messages will be used to facilitate blood sample collection at home for therapeutic drug monitoring of tacrolimus and mycophenolate. Participants will collect dried blood samples on 4 occasions. Two days in the clinical with simultaneous venipuncture (one sample) and two days at home with 4 samples collected at specified time points over 8 hours.
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
Participants will be randomized in a 1:2 allocation ratio to receive one of two text messaging interventions (basic text message reminders or more intensive bidirectional messages).
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Recipient of a kidney or kidney/pancreas transplant * Receiving immediate-release tacrolimus and mycophenolate mofetil * Willing to received text messages with a mobile device capable of receiving messages * Willing to receive standard labs at a Michigan Medicine lab draw site on 2 occasions * Ability to understand, read, and speak English * Ability to understand and willingness to sign written informed consent
Exclusion criteria
* History of multi-organ transplant (other than pancreas) * History of allergy to tape adhesives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Samples Successfully Returned for Drug Monitoring by Participants in the Unidirectional and Bidirectional Arms | 3 months | Successful home-based therapeutic drug monitoring is defined as a binary composite of 1) timely receipt (postmarked within 48 hours of planned sample collection) of samples and 2) adequate documentation of sample collection time data for pharmacokinetic analysis. Each participant in the Unidirectional and Bidirectional Text Communication arms had two opportunities for sample collection. Participants in the third arm for bioanalytical validation did not complete home sample collection and do not have results for this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Paired Samples With </=15% Difference Between Tacrolimus Concentrations Obtained Via Dried Blood and Venipuncture in the Analytical Validation Arm | 2 days | Compare concentrations of tacrolimus obtained using the two sample collection methods (dried blood and venipuncture) as measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Each participant in the analytical validation arm provided two sets of paired samples on different days. |
| Percent of Paired Samples With </=15% Difference Between Mycophenolic Acid Concentrations Obtained Via Dried Blood and Venipuncture in the Analytical Validation Arm | 2 days | Compare concentrations of mycophenolic acid obtained using the two sample collection methods (dried blood and venipuncture) as measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Each participant in the analytical validation arm provided two sets of paired samples on different days. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Unidirectional Text Reminders Participants in the unidirectional text reminder arm received automated text messages to remind them to collect blood samples 48 hours before, 12 hours before, and the morning of the planned sample collection. | 5 |
| Bidirectional Text Communication Participants in the bidirectional text communication arm received automated messages to remind them to collect blood samples 48 hours before, 12 hours before, and the morning of the planned sample collection but they were asked to confirm the planned day or reschedule. On the day of sample collection participants also replied with the time the samples are collected to trigger future reminder messages for each of the 4 samples. | 9 |
| Analytical Validation Participants in analytical validation group provided paired dried and venous blood. | 25 |
| Total | 39 |
Baseline characteristics
| Characteristic | Bidirectional Text Communication | Analytical Validation | Total | Unidirectional Text Reminders |
|---|---|---|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 8.8 | 54 years STANDARD_DEVIATION 14.4 | 53.8 years STANDARD_DEVIATION 12.5 | 52.6 years STANDARD_DEVIATION 10.2 |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment United States | 9 participants | 25 participants | 39 participants | 5 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 12 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 19 Participants | 27 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 9 | 0 / 25 |
| other Total, other adverse events | 0 / 5 | 0 / 9 | 0 / 25 |
| serious Total, serious adverse events | 0 / 5 | 0 / 9 | 0 / 25 |
Outcome results
Primary
Percent of Samples Successfully Returned for Drug Monitoring by Participants in the Unidirectional and Bidirectional Arms
Successful home-based therapeutic drug monitoring is defined as a binary composite of 1) timely receipt (postmarked within 48 hours of planned sample collection) of samples and 2) adequate documentation of sample collection time data for pharmacokinetic analysis. Each participant in the Unidirectional and Bidirectional Text Communication arms had two opportunities for sample collection. Participants in the third arm for bioanalytical validation did not complete home sample collection and do not have results for this outcome measure.
Time frame: 3 months
Population: Participants in Unidirectional and Bidirectional text communication arms
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unidirectional Text Reminders | Percent of Samples Successfully Returned for Drug Monitoring by Participants in the Unidirectional and Bidirectional Arms | 83 % of samples postmarked with 48 hrs |
| Bidirectional Text Communication | Percent of Samples Successfully Returned for Drug Monitoring by Participants in the Unidirectional and Bidirectional Arms | 100 % of samples postmarked with 48 hrs |
Secondary
Percent of Paired Samples With </=15% Difference Between Mycophenolic Acid Concentrations Obtained Via Dried Blood and Venipuncture in the Analytical Validation Arm
Compare concentrations of mycophenolic acid obtained using the two sample collection methods (dried blood and venipuncture) as measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Each participant in the analytical validation arm provided two sets of paired samples on different days.
Time frame: 2 days
Population: Participants from the analytical validation arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unidirectional Text Reminders | Percent of Paired Samples With </=15% Difference Between Mycophenolic Acid Concentrations Obtained Via Dried Blood and Venipuncture in the Analytical Validation Arm | 76 % of pairs with %difference </=15% |
Secondary
Percent of Paired Samples With </=15% Difference Between Tacrolimus Concentrations Obtained Via Dried Blood and Venipuncture in the Analytical Validation Arm
Compare concentrations of tacrolimus obtained using the two sample collection methods (dried blood and venipuncture) as measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Each participant in the analytical validation arm provided two sets of paired samples on different days.
Time frame: 2 days
Population: Participants from the analytical validation arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unidirectional Text Reminders | Percent of Paired Samples With </=15% Difference Between Tacrolimus Concentrations Obtained Via Dried Blood and Venipuncture in the Analytical Validation Arm | 80 % of pairs with %difference </=15% |