Interventional Study to Improve Adherence to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia (TAKE-IT)
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Purpose
Adherence to tyrosine kinase inhibitors is associated with improved outcomes in chronic myeloid leukemia patients. Hence, improved adherence might improve CML patients' prognosis.
Decreased adherence is a common problem in such patients, with non-adherence in up to 30% of patients in several studies. Recently, an emphasis has been placed on improving patient's adherence to tyrosine kinase inhibitors in these patients. However, there is no prospective high-quality evidence showing that adherence can be improved in these patients.
Therefore, the investigators hypothesize that adherence-encouraging interventions improve adherence to tyrosine kinase inhibitors in chronic myeloid leukemia patients.
| Condition | Intervention |
|---|---|
|
Leukemia, Myelogenous, Chronic, BCR-ABL Positive Medication Adherence |
Behavioral: Adherence-encouraging interventions - Group meeting Behavioral: Adherence-encouraging interventions - Individual meetings Behavioral: Adherence-encouraging interventions - Monthly phone calls |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label |
| Official Title: | The Effect of Active Adherence-Encouraging Interventions on Adherence to Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia - A Prospective Observational Multicenter Study (TAKE-IT) |
- Clinically relevant change in MEMS-measured adherence [ Time Frame: From 3 months before intervention, until 3 months after starting the intervention ] [ Designated as safety issue: No ]
Improvement in a patient's adherence from less than 90% during the initial 3 month run-in period, to 90% or more during the first 3 months of intervention.
Definitions:
- Adherence above 90% was defined as clinically relevant.
- Adherence rate = actual calculated dose/prescribed dose.
- Adherence will be calculated from "medical events monitoring system" (MEMS) data which will be collected continuously throughout the first 7.5 months of the study period. MEMS is an electronic monitoring system designed to compile the dosing histories of ambulatory patients prescribed oral medications
- General improvement in MEMS-measured adherence [ Time Frame: 3 months prior to the intervention, until 3 months after starting the intervention ] [ Designated as safety issue: No ]
An absolute improvement of 10% in a patient's adherence, between their adherence during the initial 3 month run-in period and their adherence during the first 3 months of intervention.
See Definitions of adherence rate and measurement of adherence in the first primary outcome description.
- Mean-difference in MEMS-measured adherence [ Time Frame: 3 months prior to intervention until 3 months after starting the intervention ] [ Designated as safety issue: No ]
Mean-difference in adherence (as measured by the MEMS) between the run-in period and the first 3 months of the intervention period (paired t-test).
The aim is to evaluate whether such a difference exists and whether it has statistical significance.
For more details on the MEMS system, please see the description under the primary outcome.
- Mean change in basal assessment of adherence scale (BAAS) [ Time Frame: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention ] [ Designated as safety issue: No ]
Mean-difference in basal assessment of adherence scale (BAAS) scores between the run-in period and the intervention period (paired t-test)
The BAAS is a clinician reported outcome which has been used to assess adherence to immunosuppressive medication in solid organ transplant patients (BAASIS; Basal assessment of adherence with the Immunosuppressive Regimen Scale). Noens et al adapted the questionnaire for use among CML patients in the ADAGIO study.
Regarding time frames:
Each questionnaire-related secondary outcome will be evaluated at two time frames:
- Short term, to assess an immediate effect on adherence
- Long term follow up (up to one year after the end of the intervention period) in order to determine whether the intervention has a long term effect on adherence.
- Effect of intervention on tyrosine kinase inhibtor related adverse events [ Time Frame: 3 months prior to intervention until 6 months after starting the intervention ] [ Designated as safety issue: No ]The incidence of tyrosine kinase inhibitor related adverse events during 6 months of intervention compared to that witnessed during the initial 3 month run-in period
- Adverse effects of tyrosine kinase inhibitors as a measure of MEMS-measured adherence [ Time Frame: 3 months prior to intervention until 3 months after starting the intervention ] [ Designated as safety issue: No ]The incidence of tyrosine kinase inhibtor related adverse events throughout the first 6 months of the study period as a function of adherence (measured by MEMS)
- Percentage of patients improving in patient self-reported non-adherence [ Time Frame: 3 months prior to intervention until 6 months after starting the intervention ] [ Designated as safety issue: No ]
The percentage of patients changing from a self-reported non-adherence of "yes" during the run-in period, to a self-reported non-adherence of "no" after the intervention, compared to the percentage of those who answered "yes" during the study period and remained "yes" after the intervention.
Definition of the "Patient self-reported question regarding non-adherence":
Each patient is asked the following question:
"It is common that patients at times miss a few doses, for a whole range of reasons. Thinking of the past 7 days have you missed any doses?"
If a patient answers 'yes' it will be taken as an indication that the patient has problems with adherence.
- Mean change in Morisky Medication Adherence Scale (MMAS) [ Time Frame: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention ] [ Designated as safety issue: No ]
Mean-difference in Morisky Medication Adherence Scale (MMAS) scores between the run-in period and the intervention period.
MMAS is a nine-item scale with scores ranging from 1 to 13, whereby higher scores reflect better adherence. The MMAS is composed of nine questions based on four themes that involve forgetfulness, negligence, interruption of drug intake after clinical improvement, and restart of drug intake when symptoms worsen.
Jonsson et al (PMID 22048790), utilized a modified version of this questionnaire in a study of TKI adherence among CML patients, and defined good adherence as a MMAS of 11 or higher.
Regarding time frames:
Each questionnaire-related secondary outcome will be evaluated at two time frames:
- Short term, to assess an immediate effect on adherence
- Long term follow up (up to one year after the end of the intervention period) in order to determine whether the intervention has a long term effect on adherence.
- Mean change in the physician visual analogue scale (VAS) of adherence [ Time Frame: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention ] [ Designated as safety issue: No ]
Mean-difference in physician visual analogue scale (VAS) of adherence scores between the run-in period and the intervention period (paired t-test).
The physician VAS on adherence rates patient adherence (as assessed by a physician) on a 10 cm VAS scale. A similar scale is in widespread use in several clinical disciplines, especially in assessing pain. It has also been used in assessing adherence to medication.
The VAS ranges from perfect adherence (100% = 100mm) to no adherence (0% = 0mm).
Regarding time frames:
Each questionnaire-related secondary outcome will be evaluated at two time frames:
- Short term, to assess an immediate effect on adherence
- Long term follow up (up to one year after the end of the intervention period) in order to determine whether the intervention has a long term effect on adherence.
- Mean change in the patient visual analogue scale (VAS) of adherence [ Time Frame: 1) Short term: 3 months prior to intervention until 6 months after starting the intervention; 2) Long term: 3 months prior to intervention until 18 months after starting the intervention ] [ Designated as safety issue: No ]
Mean-difference in patient visual analogue scale (VAS) of adherence scores between the run-in period and the intervention period (paired t-test).
The patient VAS on adherence rates patient adherence (as assessed by the patient) on a 10 cm VAS scale.
See detailed explanation on the VAS under the outcome "Mean change in the physician visual analogue scale (VAS) of adherence"
Regarding time frames:
Each questionnaire-related secondary outcome will be evaluated at two time frames:
- Short term, to assess an immediate effect on adherence
- Long term follow up (up to one year after the end of the intervention period) in order to determine whether the intervention has a long term effect on adherence.
| Estimated Enrollment: | 88 |
| Study Start Date: | April 2013 |
| Estimated Study Completion Date: | April 2015 |
| Estimated Primary Completion Date: | April 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
No Intervention: Run-in period
First 3 months of study during which adherence will be measured for each consecutively included study subject, but no intervention will be performed. Patient will receive routine treatment for CML according to the physician discretion.
|
|
|
Experimental: Adherence-encouraging period
Months 4 to 9 of study during which adherence will be measured for each consecutively included study subject, while implementing adherence-encouraging interventions:
Patient will receive routine treatment for CML according to the physician discretion. |
Behavioral: Adherence-encouraging interventions - Group meeting
One Group meeting (at the beginning of the intervention period) for all participants, focusing on issues relevant to adherence improvement
Behavioral: Adherence-encouraging interventions - Individual meetings
Individual meetings focusing on adherence issues with a multidiscilinary team
Behavioral: Adherence-encouraging interventions - Monthly phone calls
Monthly phone calls to detect urgent adherence-related issues
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients with chronic phase chronic myeloid leukemia (CP-CML), aged 18 years or older
- CP-CML defined as: Medical history of cytogenetically confirmed CP-CML defined as the presence of the Philadelphia chromosome on bone marrow aspirates (a minimum of 20 metaphases is required; FISH cannot be used). If Philadelphia chromosome was negative or if cytogenetic results were not available, BCR-ABL-positive CML patients can be included.
- At least 3 months of TKI treatment (imatinib, dasatinib or nilotinib) before recruitment.
Exclusion Criteria:
- Current or prior accelerated/blast phase or stem cell transplant
- Participation in another interventional study
- Pregnancy
Contacts and Locations| Contact: Pia Raanani, MD | +972504065447 | praanani@012.net.il |
| Contact: Avi Leader, MD | +972544437212 | avileader@yahoo.com |
| Israel | |
| Soroka Medical Center | Not yet recruiting |
| Beer Sheba, Israel, 84101 | |
| Principal Investigator: Itai Levi, MD | |
| Rambam Medical Center | Not yet recruiting |
| Haifa, Israel | |
| Principal Investigator: Noam Benyamini, MD | |
| Meir Medical Center | Not yet recruiting |
| Kfar Saba, Israel, 44281 | |
| Principal Investigator: Martin Ellis, MD | |
| Rabin Medical Center | Recruiting |
| Petah Tikva, Israel, 49100 | |
| Principal Investigator: Pia Raanani, MD | |
| Sub-Investigator: Avi Leader, MD | |
| Principal Investigator: | Pia Raanani, MD | Rabin Medical Center |
More Information
Publications:
| Responsible Party: | pia raanani, Prof. Pia Raanani, Rabin Medical Center |
| ClinicalTrials.gov Identifier: | NCT01768689 History of Changes |
| Other Study ID Numbers: | TAKE IT - CML adherence |
| Study First Received: | January 8, 2013 |
| Last Updated: | April 21, 2013 |
| Health Authority: | Israel: Ministry of Health |
Keywords provided by Rabin Medical Center:
|
adherence chronic myeloid leukemia tyrosine kinase inhibitors |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Neoplasms by Histologic Type |
Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |
ClinicalTrials.gov processed this record on May 16, 2013