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Intervention to Improve Adherence in Teen Kidney Transplant (TAKE-IT)

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ClinicalTrials.gov Identifier: NCT01356277
Recruitment Status : Completed
First Posted : May 19, 2011
Results First Posted : July 18, 2018
Last Update Posted : July 18, 2018
Sponsor:
Collaborators:
Children's Hospital of Philadelphia
Children's Hospital Medical Center, Cincinnati
Seattle Children's Hospital
Washington University School of Medicine
British Columbia Children's Hospital
The Hospital for Sick Children
St. Justine's Hospital
Temple University
Information provided by (Responsible Party):
Beth Foster, McGill University Health Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Conditions Kidney Transplantation
Medication Adherence
Interventions Behavioral: Action-focused problem-solving
Device: Electronic pillbox monitoring, dose reminders, and feedback
Enrollment 170

Recruitment Details  
Pre-assignment Details 1 patient withdrew after completing the enrollment visit, but before randomization.
Arm/Group Title Behavioral Intervention Attention Control
Hide Arm/Group Description

Participants in the intervention group will form an Adherence Support Team (AST), receive standardized adherence education, and complete behavioral intervention at 3-month intervals. In between visits, the study facilitator will maintain monthly contact with participants via short phone or text-message check-ins. The electronic pillbox will collect adherence data and will be configured to provide visual cue or text message dose reminders to participants in the intervention group. Participants in the intervention group will be fed back their electronic adherence data at each study visit.

Action-focused problem-solving: An Adherence Support Team (AST), consisting of the patient, one or both parents (or primary caregiver), and the study facilitator, will be formed for each participant in the intervention arm. "Action-focused problem-solving" is informed by two complementary behavioral approaches: problem-solving and implementation intentions.

Implementation intentions are concrete

Control participants will receive an electronic pillbox to measure medication adherence. They will meet with the study facilitator at 3-month intervals to discuss general health and life issues. The dose reminder functions of the electronic pillbox will not be enabled.
Period Title: Run-in
Started [1] 81 88
Completed [1] 76 88
Not Completed 5 0
[1]
Run-in
Period Title: Intervention Interval
Started 76 88
Completed 66 81
Not Completed 10 7
Arm/Group Title Behavioral Intervention Attention Control Total
Hide Arm/Group Description

Participants in the intervention group form an Adherence Support Team (AST), receive standardized adherence education, and complete behavioral intervention at 3-month intervals. In between visits, the study facilitator will maintain monthly contact with participants via short phone or text-message check-ins. The electronic pillbox will collect adherence data and will be configured to provide visual cue or text message dose reminders to participants in the intervention group. Participants in the intervention group will be fed back their electronic adherence data at each study visit.

Action-focused problem-solving: An Adherence Support Team (AST), consisting of the patient, one or both parents (or primary caregiver), and the study facilitator, will be formed for each participant in the intervention arm. "Action-focused problem-solving" is informed by two complementary behavioral approaches: problem-solving and implementation intentions.

Implementation intentions are concrete

Control participants will receive an electronic pillbox to measure medication adherence. They will meet with the study facilitator at 3-month intervals to discuss general health and life issues. The dose reminder functions of the electronic pillbox will not be enabled. Total of all reporting groups
Overall Number of Baseline Participants 81 88 169
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 81 participants 88 participants 169 participants
15.5
(13.2 to 17.4)
15.8
(13.3 to 17.4)
15.8
(13.2 to 17.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 88 participants 169 participants
Female
35
  43.2%
34
  38.6%
69
  40.8%
Male
46
  56.8%
54
  61.4%
100
  59.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 88 participants 169 participants
Hispanic or Latino
9
  11.1%
5
   5.7%
14
   8.3%
Not Hispanic or Latino
72
  88.9%
83
  94.3%
155
  91.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 81 participants 88 participants 169 participants
White
57
  70.4%
57
  64.8%
114
  67.5%
Black
9
  11.1%
11
  12.5%
20
  11.8%
Asian
4
   4.9%
7
   8.0%
11
   6.5%
Other
11
  13.6%
13
  14.8%
24
  14.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 88 participants 169 participants
Canada
27
  33.3%
32
  36.4%
59
  34.9%
United States
54
  66.7%
56
  63.6%
110
  65.1%
medication insurer  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 88 participants 169 participants
U.S. Public
26
  32.1%
20
  22.7%
46
  27.2%
Private
28
  34.6%
36
  40.9%
64
  37.9%
Canada provincial
27
  33.3%
32
  36.4%
59
  34.9%
household income  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 88 participants 169 participants
< $25,000
19
  23.5%
10
  11.4%
29
  17.2%
$25,000- $50,000
17
  21.0%
20
  22.7%
37
  21.9%
$51,000- $75,000
17
  21.0%
22
  25.0%
39
  23.1%
$76,000- $100,000
6
   7.4%
9
  10.2%
15
   8.9%
>$100,000
12
  14.8%
16
  18.2%
28
  16.6%
prefer not to answer
5
   6.2%
2
   2.3%
7
   4.1%
unknown
5
   6.2%
9
  10.2%
14
   8.3%
median years post-transplant  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 81 participants 88 participants 169 participants
3.7
(0.7 to 7.9)
3.0
(0.8 to 7.2)
3.1
(0.7 to 7.5)
donor source  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 88 participants 169 participants
Living
37
  45.7%
51
  58.0%
88
  52.1%
Deceased
44
  54.3%
37
  42.0%
81
  47.9%
median total lifetime duration of dialysis  
Median (Inter-Quartile Range)
Unit of measure:  Months
Number Analyzed 81 participants 88 participants 169 participants
10.0
(0.1 to 19.0)
5.0
(0 to 12.0)
6.0
(0.0 to 15.0)
primary disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 88 participants 169 participants
Congenital anomalies of the kidneys/ urinary tract
29
  35.8%
41
  46.6%
70
  41.4%
glomerulonephritis
9
  11.1%
5
   5.7%
14
   8.3%
Focal segmental glomerulosclerosis
14
  17.3%
6
   6.8%
20
  11.8%
other
29
  35.8%
36
  40.9%
65
  38.5%
number of past acute rejections  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 88 participants 169 participants
0
59
  72.8%
76
  86.4%
135
  79.9%
1
16
  19.8%
8
   9.1%
24
  14.2%
2 or more
6
   7.4%
4
   4.5%
10
   5.9%
number of comorbidities  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 88 participants 169 participants
0
41
  50.6%
43
  48.9%
84
  49.7%
at least 1
40
  49.4%
45
  51.1%
85
  50.3%
number of doses of immunosuppressives per day  
Median (Inter-Quartile Range)
Unit of measure:  Number of doses per day
Number Analyzed 81 participants 88 participants 169 participants
7
(5 to 9)
7
(5 to 9)
7
(5 to 9)
pre-intervention taking adherence  
Measure Type: Number
Unit of measure:  % days with 100% taking adherence
Number Analyzed 81 participants 88 participants 169 participants
72.8 74.7 73.8
Total Adolescent Medication Barriers scale score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 81 participants 88 participants 169 participants
37.5  (11.2) 38.1  (9.8) 37.7  (10.5)
[1]
Measure Description: A higher Adolescent medication Barriers Scale (AMBS) represents a greater burden of barriers. The possible range for total score is 17-85.
1.Primary Outcome
Title Taking Adherence
Hide Description

Daily "taking adherence", defined as the percentage of prescribed doses taken each day (as measured by electronic monitoring). The daily taking adherence score could take a value of 0%, 50%, or 100% for patients on twice daily dosing, and 0% or 100% for patients on once daily dosing. Each patient had a taking adherence score for every day of observation (repeated measures). On days that the pillbox was not in use due to technical problems or participant non-use (due to travel etc), no score was given.

To summarize adherence for each arm, we calculated the total percentage of days of observation for which there was 100% taking adherence. The denominator for this calculation was the the total number of days of observation of each participant, summed across all participants; the numerator was the total number of days of observation of each participant for which taking adherence was 100%, summed across all participants.

Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
We used unadjusted ordinal logistic regression with generalized estimating equations to account for repeated measures (i.e. score on each day) to compare taking and timing adherence between the intervention and control groups during the intervention interval. An additional ‘as-treated’ analysis was also conducted. All available data were included.
Arm/Group Title Behavioral Intervention Attention Control
Hide Arm/Group Description:

The patient, parent and Coach formed an Adherence Support Team. The Coach delivered standardized education on immunosuppressive medications, identified adherence barriers using the AMBS/PMBS and the last 3 months of electronic monitoring data and then used ‘Action-Focused Problem-Solving’ to address barriers selected as most important by the patient.

Action-focused problem-solving involved brainstorming possible solutions to a barrier, rating the potential solutions, and selecting one solution to implement following the session. The solution was concrete and took the form of an “If/when…then…” statement. Intervention participants could choose to receive text message, email, or visual cue dose reminders. At subsequent sessions the Coach, patient, and parent jointly reviewed the electronic adherence monitoring data from the prior 3 mo to identify adherence patterns and guide the development and revision of action plans.

Control group study visits were conducted at the same intervals as intervention visits and consisted of the Coach engaging in active listening and providing non-specific support only. Adherence was NOT discussed with control participants.
Overall Number of Participants Analyzed 64 74
Measure Type: Number
Unit of Measure: % of days with 100% taking adherence
78 68
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Behavioral Intervention, Attention Control
Comments We estimated a sample size of 75 participants per group to have 85% power to detect a 20% difference in taking adherence between groups, using 2–sided tests and setting alpha at 0.05, assuming a common standard deviation of 40%. Targeted enrollment of 176 participants accounted for 15% drop-out. Only participants with electronic pillbox data could be included. For participants who withdrew or stopped using the pillbox, all available pillbox data were included.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Regression, Logistic
Comments Unadjusted, ordinal logistic regression
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.66
Confidence Interval (2-Sided) 95%
1.15 to 2.39
Estimation Comments An odds ratio greater than 1.0 indicates higher adherence in Intervention participants compared with controls.
2.Primary Outcome
Title Timing Adherence
Hide Description

Daily "timing adherence", defined as the percentage of doses taken within 1 hour before to 2 hours after the prescribed dosing time each day (as measured by electronic monitoring). The daily timing adherence score could take a value of 0%, 50%, or 100% for patients on twice daily dosing, and 0% or 100% for patients on once daily dosing. Each patient had a timing adherence score for every day of observation (repeated measures). On days that the pillbox was not in use due to technical problems or participant non-use (due to travel etc), no score was given.

To summarize timing adherence for each arm, we calculated the total percentage of days of observation for which there was 100% timing adherence. The denominator for this calculation was the the total number of days of observation of each participant, summed across all participants; the numerator was the total number of days of observation of each participant for which timing adherence was 100%, summed across all participants.

Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
We used unadjusted ordinal logistic regression with generalized estimating equations to account for repeated measures (i.e. score on each day) to compare timing adherence between the intervention and control groups during the intervention interval. An additional ‘as-treated’ analysis was also conducted. All available data were included.
Arm/Group Title Behavioral Intervention Attention Control
Hide Arm/Group Description:

The patient, parent and Coach formed an Adherence Support Team. The Coach delivered standardized education on immunosuppressive medications, identified adherence barriers using the AMBS/PMBS and the last 3 months of electronic monitoring data and then used ‘Action-Focused Problem-Solving’ to address barriers selected as most important by the patient.

Action-focused problem-solving involved brainstorming possible solutions to a barrier, rating the potential solutions, and selecting one solution to implement following the session. The solution was concrete and took the form of an “If/when…then…” statement. Intervention participants could choose to receive text message, email, or visual cue dose reminders. At subsequent sessions the Coach, patient, and parent jointly reviewed the electronic adherence monitoring data from the prior 3 mo to identify adherence patterns and guide the development and revision of action plans.

Control group study visits were conducted at the same intervals as intervention visits and consisted of the Coach engaging in active listening and providing non-specific support only. Adherence was NOT discussed with control participants.
Overall Number of Participants Analyzed 64 74
Measure Type: Number
Unit of Measure: % of days with 100% timing adherence
73 61
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Behavioral Intervention, Attention Control
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Regression, Logistic
Comments Unadjusted ordinal logistic regression
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.74
Confidence Interval (2-Sided) 95%
1.21 to 2.50
Estimation Comments An odds ratio greater than 1.0 indicates higher adherence in Intervention participants compared with controls.
3.Secondary Outcome
Title Standard Deviation (SD) of Tacrolimus Trough Levels
Hide Description The SD of all tacrolimus trough levels done for clinical care (except during hospitalizations or illnesses) were calculated for participants with >=3 tacrolimus levels.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Behavioral Intervention Standard Care
Hide Arm/Group Description:
Participants met with the coach at 3-month intervals. At each visit they had the opportunity to revise their Action plan or generate a new one. Action plans were concrete plans to address an adherence barrier that took the form "When... then..."
Participants in the control group met with the coach at 3-month intervals but did not discuss adherence. They received general social support.
Overall Number of Participants Analyzed 58 63
Median (Inter-Quartile Range)
Unit of Measure: standard deviation units
1.6
(0.9 to 2.5)
1.4
(0.9 to 2.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Behavioral Intervention, Standard Care
Comments Null hypothesis was that there was no difference in the SD of tacrolimus trough levels between intervention and control.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.49
Comments [Not Specified]
Method Wilcoxon ranksum
Comments [Not Specified]
4.Secondary Outcome
Title Self-reported Taking Adherence
Hide Description Self-reported taking adherence, assessed using the Medical Adherence Measure- Medication Module (MAM-MM), was scored as the proportion of doses taken in the previous week. MAM-MM scores for each patient were summarized as the mean of the four scores post-intervention.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
included all those who participated during the intervention interval
Arm/Group Title Behavioral Intervention Standard Care
Hide Arm/Group Description:
Participants met with the coach at 3-month intervals. At each visit they had the opportunity to revise their Action plan or generate a new one. Action plans were concrete plans to address an adherence barrier that took the form "When... then..."
Participants in the control group met with the coach at 3-month intervals but did not discuss adherence. They received general social support.
Overall Number of Participants Analyzed 76 88
Mean (Standard Deviation)
Unit of Measure: percentage of prescribed doses taken
98.3  (4.5) 97.1  (6.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Behavioral Intervention, Standard Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Self-reported Timing Adherence
Hide Description Self-reported timing adherence, assessed using the Medical Adherence Measure- Medication Module (MAM-MM), was scored as the proportion of doses taken up to 2 hours after the prescribed time in the previous week. MAM-MM scores for each patient were summarized as the mean of the four scores post-intervention.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
included all those who participated during the intervention interval
Arm/Group Title Behavioral Intervention Standard Care
Hide Arm/Group Description:
Participants met with the coach at 3-month intervals. At each visit they had the opportunity to revise their Action plan or generate a new one. Action plans were concrete plans to address an adherence barrier that took the form "When... then..."
Participants in the control group met with the coach at 3-month intervals but did not discuss adherence. They received general social support.
Overall Number of Participants Analyzed 76 88
Mean (Standard Deviation)
Unit of Measure: percentage of doses taken on time
95.0  (7.9) 92.9  (9.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Behavioral Intervention, Standard Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Acute Rejection Rate
Hide Description The acute rejection rate, measured as rejections per 100 person-years of observation.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
included all those who participated during the intervention interval
Arm/Group Title Behavioral Intervention Standard Care
Hide Arm/Group Description:
Participants met with the coach at 3-month intervals. At each visit they had the opportunity to revise their Action plan or generate a new one. Action plans were concrete plans to address an adherence barrier that took the form "When... then..."
Participants in the control group met with the coach at 3-month intervals but did not discuss adherence. They received general social support.
Overall Number of Participants Analyzed 76 88
Measure Type: Number
Unit of Measure: events per 100 person-years
1.06 1.69
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Behavioral Intervention, Standard Care
Comments Rates were compared between intervention and control groups using Chi square
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
7.Secondary Outcome
Title Annualized Change in Estimated Glomerular Filtration Rate (eGFR)
Hide Description Change in estimated glomerular filtration rate, estimated using the Schwartz equation for those < 18 y. and the CKD-EPI equation for those 18y and older, standardized to a 12-month period.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
included all those with eGFR data available
Arm/Group Title Behavioral Intervention Standard Care
Hide Arm/Group Description:
Participants met with the coach at 3-month intervals. At each visit they had the opportunity to revise their Action plan or generate a new one. Action plans were concrete plans to address an adherence barrier that took the form "When... then..."
Participants in the control group met with the coach at 3-month intervals but did not discuss adherence. They received general social support.
Overall Number of Participants Analyzed 66 81
Median (Inter-Quartile Range)
Unit of Measure: ml/min/1.73m^2
-2.3
(-10.6 to 2.3)
-3.3
(-7.7 to 3.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Behavioral Intervention, Standard Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .45
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 12 months
Adverse Event Reporting Description The standard definitions were used.
 
Arm/Group Title Multi-component Intervention Attention Control
Hide Arm/Group Description
  • Adherence Support Team (patient, parent, Coach)
  • standardized education on immunosuppressive medications
  • identification of adherence barriers
  • Electronic adherence monitoring with feedback of past 3 months of electronic monitoring data at 3-month intervals
  • 'Action-Focused Problem-Solving' to address barriers selected as most important by the patient
  • text message, email, or visual cue dose reminders
  • Electronic adherence monitoring
  • meetings with Coach at 3 month intervals
All-Cause Mortality
Multi-component Intervention Attention Control
Affected / at Risk (%) Affected / at Risk (%)
Total   0/76 (0.00%)      0/88 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Multi-component Intervention Attention Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/76 (31.58%)      30/88 (34.09%)    
Blood and lymphatic system disorders     
PTLD *  0/76 (0.00%)  0 1/88 (1.14%)  2
General disorders     
Hospitalizations *  24/76 (31.58%)  42 29/88 (32.95%)  54
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Multi-component Intervention Attention Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   42/76 (55.26%)      52/88 (59.09%)    
Gastrointestinal disorders     
vomiting/diarrhea *  4/76 (5.26%)  5 3/88 (3.41%)  3
General disorders     
Abdominal pain *  4/76 (5.26%)  5 7/88 (7.95%)  8
Infections and infestations     
CMV infection *  4/76 (5.26%)  5 0/88 (0.00%)  0
influenza infection *  3/76 (3.95%)  3 5/88 (5.68%)  5
other infection *  14/76 (18.42%)  20 21/88 (23.86%)  31
Renal and urinary disorders     
acute rejection *  8/76 (10.53%)  9 10/88 (11.36%)  17
Surgical and medical procedures     
surgery/procedure *  5/76 (6.58%)  7 6/88 (6.82%)  6
*
Indicates events were collected by non-systematic assessment
Patients who withdrew or ceased to use the pillbox may introduce bias if they represented patients who were more or less adherent than those who continued to use the pillbox.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Bethany Foster
Organization: McGill University Health Centre
Phone: 514-412-4461
Responsible Party: Beth Foster, McGill University Health Center
ClinicalTrials.gov Identifier: NCT01356277     History of Changes
Other Study ID Numbers: R01DK092977-01 ( U.S. NIH Grant/Contract )
First Submitted: May 17, 2011
First Posted: May 19, 2011
Results First Submitted: April 23, 2018
Results First Posted: July 18, 2018
Last Update Posted: July 18, 2018