Clinical trial NCT02402140: Influence of Pharmaceutical Care on the Intraindividual Variability of Tacrolimus Concentrations
Official title: A Prospective Randomized Trial Investigating the Influence of Pharmaceutical Care on the Intraindividual Variability of Tacrolimus Concentrations Early After Kidney Transplant.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Renal Transplant Graft Failure
Keywords: tacrolimus blood concentration
pharmaceutical intervention
intrasubject variability
Lead sponsor: Hospital do Rim e Hipertensão
Sponsor class: OTHER
First posted: 2015-03-30
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: Primary end-point

The primary end-point was the influence of pharmaceutical intervention in tacrolimus intra-subject variability during the first 3 months after kidney transplant. Coefficients of variation were calculated from the average of dose-corrected tacrolimus blood concentration(CV= Standard Deviation (SD) x 100/mean) of study visits day 10, 14, 21, 30, 60 and 90 post kidney transplant.

Secondary end-points

1. Secondary outcomes included evaluate percentage of patients who achieved target levels of tacrolimus in day study visits 7, 10, 14, 21, 28, 60 e 90 days after kidney transplant;
2. Tacrolimus bioavailability profile during the period of 3 months,characterized by mean and standard deviation (SD) of dose corrected tacrolimus blood concentration(ng/ml/mg);
3. Assess patient adherence through validated questionnaire "Portuguese version of Basel Scale Adherence Rating Immunosuppressive Drugs (BAASIS) scale". It consists of a four-item questionnaire measuring nonadherence to immunosuppressives over the past four weeks. This questionnaire assesses omission of single doses or successive doses, timing deviations \>2h and dose reductions. Responses are given on a six-point scale: never, once per month, every second week, every week, more than once per week and every day. Patients that answer different from "never" in any of the four questions are considered as nonadherent;
4. We evaluated renal function eGFR by Modification of Diet in Renal Disease (MDRD);
5. We evaluated Incidence of Infections;
6. We evaluated Treated acute rejection episodes;
7. We evaluated Death cases;
8. We evaluated Graft loss cases;
9. We evaluated Discontinuation of immunosuppressive treatment;
10. We evaluated Hospital readmissions.

Study Design

This was a single-center, prospective, randomized and controlled study to evaluate the influence of pharmaceutical intervention in tacrolimus intra-subject variability during the first 3 months after transplantation. The authors designed the protocol, acquired and maintained the data, and conducted the statistical analysis. The protocol was approved by an independent ethics committee. All subjects signed a written informed consent before enrollment and the study was conducted according to good clinical practices and declaration of Helsinki. This study was conducted at Hospital do Rim between February 2014 and December 2014, 128 randomized and were followed for 3 months after transplantation.

Detailed description: Population

Inclusion criteria were patients who underwent renal transplantation aged ≥18 years old, who signed the informed consent, who underwent follow-up post transplant clinic at the Hospital do Rim for 3 months, receiving immunosuppressive drugs tacrolimus, prednisone and sodium mycophenolate or tacrolimus, azathioprine, and prednisone. Exclusion criteria were patients who underwent second kidney transplant, which did not follow the Hospital do Rim after transplant and who were participating in some other study with pharmaceutical intervention.

Randomization The randomization plan was carried out in blocks and stratified by immunosuppressive drugs tacrolimus, prednisone and mycophenolate sodium or tacrolimus, prednisone and azathioprine.

Opaque envelopes were made from a table of random numbers and they were open on the day of randomization to determine the group to which each patient was allocated group 1 with pharmaceutical intervention or group 2 without pharmaceutical intervention.

Eligibility criteria: Inclusion Criteria:

* patients who underwent renal transplantation aged ≥18 years old,
* who signed the informed consent,
* who underwent follow-up post transplant clinic at the Hospital do Rim for 3 months,
* receiving immunosuppressive drugs tacrolimus, prednisone and sodium mycophenolate or tacrolimus, azathioprine, and prednisone.

Exclusion Criteria:

* were patients who underwent second kidney transplant,
* which did not follow the Hospital do Rim after transplant and who were participating in some other study with pharmaceutical intervention.

Primary outcomes:
measure: The primary end-point was the influence of pharmaceutical intervention in tacrolimus intra-subject variability during the first 3 months after kidney transplant. variability during the first 3 months after transplantation.
timeFrame: 3 months
Secondary outcomes:
measure: Assess patient adherence through validated questionnaire "Portuguese version of BAASIS scale (Basel Scale Adherence Rating Immunosuppressive Drugs)";
timeFrame: 3 months
measure: Secondary outcomes included evaluate percentage of patients who achieved target levels of tacrolimus in day study visits day 7, 10, 14, 21, 28, 60 e 90 post kidney transplant
timeFrame: 3 months
measure: We also evaluated renal function (eGFR by MDRD formula)
timeFrame: 3 months
measure: Tacrolimus bioavailability profile during the period of 3 months
timeFrame: 3 months
measure: We evaluated the incidence of Infections
timeFrame: 3 months
measure: We evaluated treated acute rejection episodes
timeFrame: 3 months
measure: We evaluated death cases
timeFrame: 3 months
measure: We evaluated graft loss cases
timeFrame: 3 months
measure: We evaluated discontinuation of immunosuppressive treatment
timeFrame: 3 months
measure: We evaluated hospital readmissions.
timeFrame: 3 months
Other outcomes:
Locations:
Study officials:
affiliation: Hospital do Rim
name: Adrieli BA Bessa, Pharmacist
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 12;9(9):CD012854. doi: 10.1002/14651858.CD012854.pub2.