Improving Adherence in Nonadherent Kidney Transplant Patients

Kidney Transplantation Clinical Trial

Official title:

A Pharmacist Led, Patient Tailored Intervention to Improve Immunosuppressant Medication Adherence in Nonadherent Kidney Transplant Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03892317
• Other study ID #: 17HH4287
• Status: Completed
• Phase: N/A
• Start date: May 14, 2018
• Est. completion date: July 27, 2020

Study information

• Verified date: July 2020
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Organs for transplantation remain a scarce and precious resource with over 5000 patients currently on the kidney transplant waiting list. A kidney transplant costs approximately £17,000 in the first year and £5,000 per subsequent year. If the transplant fails, the patient must return to dialysis at an estimated cost of £30,800 per year or be retransplanted. While short term outcomes have improved steadily over the last 15-20 years, longer term outcomes haven't and after 10 years approximately 30% of kidney transplants have failed. Nonadherence to immunosuppressive medication is increasingly being associated with these poor long term outcomes and studies have estimated that 30- 50% of transplant patients are nonadherent to their immunosuppressive medication. The investigators want to determine whether immunosuppression medication adherence can be improved in a group of patients receiving tailored medication adherence support form a pharmacist. Adherence support will be provided for one year and will be individualised to each patient in the intervention group after identifying both their practical and perceptual barriers to adherence. The adherence interventions offered may include additional education and medication counselling, setting alarms, provision of a medication list, the use of a medications adherence app on a smart phone, reducing the number and frequency of tablets a patient takes or referral on to another health professional such as a social worker or psychologist for additional support. A range of clinical outcomes will be assessed for all patients on a regular basis in order to determine whether the provision of effective medication adherence support for our kidney transplant patients may help to optimise the long-term outcomes of these transplants

Description:

This study will be undertaken using a prospective, multidimensional design. 42 nonadherent kidney transplant patients will be included in the intervention group. The nonadherent patients will be identified through Imperial College Renal and Transplant Centre (ICRTC) Outpatient Clinic based at Hammersmith Hospital. Standard and transplant specific demographics will be collected for all patients. All kidney transplant patients have their tacrolimus levels measured at each clinic visit. The variability of these levels can be used as a marker of their adherence. Patients with a high intrapatient variability (IPV) of their levels are said to be nonadherent. The Chief Investigator or another member of the research team will approach individual patients directly in the transplant out-patient clinic where they are members of the multidisciplinary clinical care team. The Chief Investigator or another member of the research team may also telephone patients to invite them to clinic to discuss participation in the trial. The Chief Investigator or another member of the research team will describe the study to the patient, answer any questions they have and provide them with a participant information sheet (PIS). Patients will be given the opportunity to take the PIS away and think about whether they would like to participate. A follow up discussion either in clinic or on the phone will be arranged with the patient to answer any queries they have within two weeks of providing them with the PIS; during that discussion, the Chief Investigator or other member of the research team will arrange an appointment in the transplant clinic with the patient to sign the consent form if they do decide to participate. Patients recruited into the study will receive pharmacist led, patient tailored interventions to improve immunosuppressant medication adherence. Patients will be included in the study for one year from recruitment.

The pharmacist led, patient tailored intervention will involve regular, intensive, personalised support from a pharmacist to improve adherence to immunosuppressive medications. The pharmacist will meet with the patient on a regular basis in the transplant clinic to identify their perceptual and practical barriers to adherence and agree a support plan that is tailored to them.

Within the first two weeks of recruitment, the study pharmacist will meet with the patient in transplant clinic to:

• Undertake a full medication history

• Discuss self-reported medication nonadherence

• Undertake the BAASIS questionnaire

• Ask the patient to complete a Beliefs about Medicines Questionnaire (BMQ)

• Undertake a socioeconomic and educational assessment

• Undertake to gain collateral reporting of nonadherence by clinicians, relatives, friends or carers

• Perform a tacrolimus pill count

• Check in-house dispensing records of tacrolimus

• Identify barriers to adherence

• Tailor interventions and support to the needs of the patient

• Complete a motivational interview

• Agree to meet again during an outpatient clinic visit within an agreed time which is appropriate for the patient needs and within 3 months.

This first visit will provide a baseline assessment of the patient's medication adherence.

Tailored support may include:

• Setting alarms

• Medication diary card or calendar

• Medication compliance aid filled by the patient, family/carers or by a pharmacy professional

• Adherence app

• Reducing the complexity of the medication regime

• Positioning medication within their daily routine eg. by toothbrush

• Changing formulations

• Additional education regarding need for medication / timing of doses

• Referral to a social worker to assist with affordability of medicines

• Referral to a psychologist to explore deeper psychological issues regarding medicines taking

The structure of each follow up adherence review will be the same as the first formal adherence review with the exception that the BMQ will only be repeated at the end of the one year follow-up and the socioeconomic and educational assessment will only be undertaken at the first assessment review. Every patient will have a formal adherence assessment at recruitment and then at 3, 6, 9 and 12 months. At the end of one year of follow-up, the specific benefits perceived by the patient of intensive adherence support from a pharmacist will be determined through a questionnaire.

Baseline nonadherence will be measured at the first visit with the study pharmacist within two weeks of recruitment and then at 3, 6, 9 and 12 months. The IPV of their tacrolimus levels and their outpatient clinic nonattendance rate will be measured retrospectively in the 12 months prior to recruitment to the study and then prospectively at the end of the intervention year. The IPV is calculated from the tacrolimus levels measured for an individual patient using the coefficient of variance mathematical formula - Coefficient of variance (COV) defined as: SD x 100 / Mean. The outpatient clinic nonattendance for each participant will be taken from the hospital integrated computer system.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 27, 2020
• Est. primary completion date: July 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult kidney transplant patients (18 years of age and above)

• Kidney transplant patients with an IPV of tacrolimus levels of greater than 18.15% in the previous 12 months

Exclusion Criteria:

• Antibody incompatible transplants including patients with preformed HLA and blood group incompatible

• Previous rejection

• Donor specific antibody positive

• HIV positive patients

• Simultaneous pancreas and kidney patients

• Paediatric patients (less than 18 years of age)

Related Conditions & MeSH terms

• Kidney Transplantation
• Medication Adherence

Intervention

Behavioral:
• Pharmacist led medication adherence interventions
Medication adherence interventions which will be tailored to individual patient need

Locations

Country	Name	City	State
United Kingdom	Imperial College Renal and Transplant Centre	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (18)

Butler JA, Roderick P, Mullee M, Mason JC, Peveler RC. Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review. Transplantation. 2004 Mar 15;77(5):769-76. — View Citation

De Bleser L, Matteson M, Dobbels F, Russell C, De Geest S. Interventions to improve medication-adherence after transplantation: a systematic review. Transpl Int. 2009 Aug;22(8):780-97. doi: 10.1111/j.1432-2277.2009.00881.x. Epub 2009 Apr 6. Review. — View Citation

Denhaerynck K, Steiger J, Bock A, Schäfer-Keller P, Köfer S, Thannberger N, De Geest S. Prevalence and risk factors of non-adherence with immunosuppressive medication in kidney transplant patients. Am J Transplant. 2007 Jan;7(1):108-16. Epub 2006 Nov 15. — View Citation

Dew MA, DiMartini AF, De Vito Dabbs A, Myaskovsky L, Steel J, Unruh M, Switzer GE, Zomak R, Kormos RL, Greenhouse JB. Rates and risk factors for nonadherence to the medical regimen after adult solid organ transplantation. Transplantation. 2007 Apr 15;83(7 — View Citation

Fine RN, Becker Y, De Geest S, Eisen H, Ettenger R, Evans R, Rudow DL, McKay D, Neu A, Nevins T, Reyes J, Wray J, Dobbels F. Nonadherence consensus conference summary report. Am J Transplant. 2009 Jan;9(1):35-41. doi: 10.1111/j.1600-6143.2008.02495.x. Rev — View Citation

Gaston RS, Hudson SL, Ward M, Jones P, Macon R. Late renal allograft loss: noncompliance masquerading as chronic rejection. Transplant Proc. 1999 Jun;31(4A):21S-23S. — View Citation

Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl 3:S1-155. doi: 10.1111/j.1600-6143.2009.02834.x. — View Citation

Massey EK, Tielen M, Laging M, Beck DK, Khemai R, van Gelder T, Weimar W. The role of goal cognitions, illness perceptions and treatment beliefs in self-reported adherence after kidney transplantation: a cohort study. J Psychosom Res. 2013 Sep;75(3):229-3 — View Citation

Massey EK, Tielen M, Laging M, Timman R, Beck DK, Khemai R, van Gelder T, Weimar W. Discrepancies between beliefs and behavior: a prospective study into immunosuppressive medication adherence after kidney transplantation. Transplantation. 2015 Feb;99(2):3 — View Citation

Morrissey PE, Flynn ML, Lin S. Medication noncompliance and its implications in transplant recipients. Drugs. 2007;67(10):1463-81. Review. — View Citation

Morrissey PE, Reinert S, Yango A, Gautam A, Monaco A, Gohh R. Factors contributing to acute rejection in renal transplantation: the role of noncompliance. Transplant Proc. 2005 Jun;37(5):2044-7. — View Citation

Pinsky BW, Takemoto SK, Lentine KL, Burroughs TE, Schnitzler MA, Salvalaggio PR. Transplant outcomes and economic costs associated with patient noncompliance to immunosuppression. Am J Transplant. 2009 Nov;9(11):2597-606. doi: 10.1111/j.1600-6143.2009.027 — View Citation

Prendergast MB, Gaston RS. Optimizing medication adherence: an ongoing opportunity to improve outcomes after kidney transplantation. Clin J Am Soc Nephrol. 2010 Jul;5(7):1305-11. doi: 10.2215/CJN.07241009. Epub 2010 May 6. Review. — View Citation

Roberts DM, Jiang SH, Chadban SJ. The treatment of acute antibody-mediated rejection in kidney transplant recipients-a systematic review. Transplantation. 2012 Oct 27;94(8):775-83. doi: 10.1097/TP.0b013e31825d1587. Review. — View Citation

Schäfer-Keller P, Steiger J, Bock A, Denhaerynck K, De Geest S. Diagnostic accuracy of measurement methods to assess non-adherence to immunosuppressive drugs in kidney transplant recipients. Am J Transplant. 2008 Mar;8(3):616-26. doi: 10.1111/j.1600-6143.2007.02127.x. — View Citation

Sellarés J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012 F — View Citation

Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, Goldberg A, Birk PE, Rush DN, Nickerson PW. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant. 2012 May;12(5): — View Citation

Wiebe C, Nevins TE, Robiner WN, Thomas W, Matas AJ, Nickerson PW. The Synergistic Effect of Class II HLA Epitope-Mismatch and Nonadherence on Acute Rejection and Graft Survival. Am J Transplant. 2015 Aug;15(8):2197-202. doi: 10.1111/ajt.13341. Epub 2015 J — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in immunosuppression medication adherence before and after the intervention	Medication adherence will be assessed and compared using the BAASIS questionnaire at recruitment and at the end of the study. The BAASIS questionnaire is validated for assessing immunosuppression nonadherence in transplant patients. Any patient answering yes to any of the questions is assessed to be nonadherent	One year
Primary	Change in the median IPV before and after the intervention	Intrapatient variability of tacrolimus levels will be measured and compared	One year
Primary	Change in outpatient clinic nonattendance rate before and after the intervention	Outpatient clinic nonattendance rate will be assessed and compared during the 12 months prior to recruitment to the study and during the study	One year
Secondary	Biopsy proven ACR / AMR	Number of patients who develop biopsy proven ACR/AMR	One year
Secondary	The number of readmissions	The number of readmissions and their reasons why during the study will be recorded	One year
Secondary	Donor specific antibody (DSA) or transplant glomerulopathy	Number of patients who develop a DSA or transplant glomerulopathy (CNI) toxicity or diabetic change on biopsy	One year
Secondary	Fibrosis, hyalinosis, calcineurin inhibitor (CNI) toxicity or diabetic change on toxicity	Number of patients who develop fibrosis, hyalinosis, calcineurin inhibitor	One year
Secondary	Graft loss	Number of patients who lose their graft	One year
Secondary	Death	Number of patients who die	One year
Secondary	Serum creatinine	Change in serum creatinine at the end of the study	One year
Secondary	eGFR	Change in eGFR at the end of the study	One year
Secondary	Proteinuria	Change in proteinuria at the end of the study	One year
Secondary	Haematocrit	Change in haematocrit at the end of the study	One year
Secondary	Haemoglobin	Change in haemoglobin at the end of the study	One year
Secondary	Albumin	Change in albumin at the end of the study	One year
Secondary	Tacrolimus levels	Change in tacrolimus levels at the end of the study	One year