Rosuvastatin adherence app study in China - eHELP China

Study identifier:D3560C00088

ClinicalTrials.gov identifier:NCT02433288

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A randomized, two-arm, open, 24-week study to evaluate the effect of a smart phone-based patient support tool on duration of treatment in patients prescribed rosuvastatin in China

Medical condition

Dyslipidemia

Phase

N/A

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

885

Study type

Interventional

Age

18 Years - 80 Years

Date

Study Start Date: 20 Jul 2015

Primary Completion Date: 28 Oct 2016

Study Completion Date: 28 Oct 2016

Study design

Allocation: Randomized
Endpoint Classification: Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care

Verification:

Verified 01 Aug 2018 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

-Provision of informed consent prior to any study specific procedures
-Female or male aged 18-80 years, diagnosed with dyslipidemia or hyperlipidemia at high risk and prescribed rosuvastatin
Dyslipidemia or hyperlipidemia defined as:
LDL-C≥2.6 mmol/L and TG<4.52mmol/L
High risk complies with any of the following:
• Documented cardiovascular disease (CVD) by invasive or non-invasive testing (such as coronary angiography, nuclear imaging, stress echocardiography, carotid plaque on ultrasound), previous myocardial infarction (MI), acute coronary syndrome (ACS), coronary revascularization [percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG)] and other arterial revascularization procedures, ischaemic stroke and peripheral arterial disease (PAD).
• Patients with type 2 diabetes, patients with type 1 diabetes with target organ damage (such as microalbuminuria).
• Patients with moderate to severe chronic kidney disease [(CKD), glomerular filtration rate (GFR) < 60 mL/min/1.73 m2].
-Patients must have a smart phone that is compatible with the patient support tool and clinical evaluation questionnaire at their disposal and are comfortable with using of interactive smart phone applications. The required specification for the phone will be determined after completed testing.
-Ability to read, understand and write Chinese.
-Statin-naïve or with no statin use during the last 4 weeks prior to enrolment except in the event of patients may receive at most 7 doses of statins during current hospitalization before enrollment.

Exclusion Criteria

-Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
-Previous enrolment or randomisation in the present study
-Participation in another clinical study with an investigational product or device during the last 30 days excluding prospective/retrospective register based studies that do not require any extra visits in addition to ordinary health care. Patients who withdraw from this study for any reason cannot re-enter the study.
-Patients in whom rosuvastatin is contraindicated i.e.
• patients with hypersensitivity to rosuvastatin or any of the excipients.
• patients with active liver disease including unexplained, persistent elevations of serum transaminases and have serum transaminase elevation exceeding 3 x the upper limit of normal (ULN).
• patients with severe renal impairment (creatinine clearance <30 ml/min).
• patients with myopathy.
• patients receiving concomitant cyclosporin.
• females during pregnancy and lactation and women of childbearing potential who are not using appropriate contraceptive measures.
-Significant medical or psychological condition that, in the opinion of the Investigator, would compromise the patient’s safety or successful participation in the study.

Location

Research Site

Beijing, China, 100045

Location

Research Site

Tianjin, China, 300192

Location

Research Site

Beijing, China, 100029

Location

Research Site

Beijing, China, 101199

Location

Research Site

Shanghai, China, 200072

Location

Research Site

Tianjin, China, 300211

Location

Research Site

Beijing, China, 100730

Location

Research Site

Shanghai, China, 201199

Arms	Assigned Interventions
Other: Active app The smart phone application used on the patients’ smart phones will contain both the patient support tool and the questions for the clinical evaluation in the form of the Rosuvastatin Adherence questionnaire (RAQ), Beliefs about Medicine Questionnaire - General (BMQ-G), (Horne, 1999) and a Lifestyle questionnaire (LSQ) on disease understanding, lifestyle and treatment awareness. Patients in the Active group will also receive feedback on their daily rosuvastatin treatment as entered in the patient support tool.	Other: Smart phone based patient support tool The smart phone application used on the patients’ smart phones will contain both the patient support tool and the questions for the clinical evaluation in the form of the Rosuvastatin Adherence questionnaire (RAQ), Beliefs about Medicine Questionnaire - General (BMQ-G), (Horne, 1999) and a Lifestyle questionnaire (LSQ) on disease understanding, lifestyle and treatment awareness. Patients in the Active group will also receive feedback on their daily rosuvastatin treatment as entered in the patient support tool. Other Name: Active
Other: Control app a smart phone application will be used to prompt patients with the questions for the clinical evaluation (RAQ, BMQ-G and LSQ).	Other: Control application: only for data collection the patients will have no access to the smart phone-based patient support tool. However, a smart phone application will be used to prompt patients with the questions for the clinical evaluation (RAQ, BMQ-G and LSQ). Other Name: Control

Arms

Assigned Interventions

Other: Active app
The smart phone application used on the patients’ smart phones will contain both the patient support tool and the questions for the clinical evaluation in the form of the Rosuvastatin Adherence questionnaire (RAQ), Beliefs about Medicine Questionnaire - General (BMQ-G), (Horne, 1999) and a Lifestyle questionnaire (LSQ) on disease understanding, lifestyle and treatment awareness. Patients in the Active group will also receive feedback on their daily rosuvastatin treatment as entered in the patient support tool.

Other: Smart phone based patient support tool
The smart phone application used on the patients’ smart phones will contain both the patient support tool and the questions for the clinical evaluation in the form of the Rosuvastatin Adherence questionnaire (RAQ), Beliefs about Medicine Questionnaire - General (BMQ-G), (Horne, 1999) and a Lifestyle questionnaire (LSQ) on disease understanding, lifestyle and treatment awareness. Patients in the Active group will also receive feedback on their daily rosuvastatin treatment as entered in the patient support tool.

Other Name: Active

Other: Control app
a smart phone application will be used to prompt patients with the questions for the clinical evaluation (RAQ, BMQ-G and LSQ).

Other: Control application: only for data collection
the patients will have no access to the smart phone-based patient support tool. However, a smart phone application will be used to prompt patients with the questions for the clinical evaluation (RAQ, BMQ-G and LSQ).

Other Name: Control

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
885 patients signed Inform Consent and were randomized in the study, 443 subjects in the active group and 442 subjects in the control group. 320 (72.2%) and 316 (71.5%) patients, respectively, completed the study. The overall completion rate was 71.9%. 31 patients (12 and 19 respectively) was not successful in receiving the relevant application.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 885 patients were randomized (1:1) to two groups: an active group which received the smart phone-based patient support tool and a control application used for data collection only.

Reporting Groups

	Description
Active group	receive the smart phone-based patient support tool
Control group	provided only the control application and not the smart phone-based patient support tool

Participant Flow: Overall Study

	Active group	Control group
STARTED	443	442
COMPLETED	320	316
NOT COMPLETED	123	126
Severe non-compliance to protocol	13	7
Eligibility criteria not fullfilled	7	3
Withdrawal by Subject	101	99
Lost to Follow-up	2	14
Death	0	3

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The baseline characteristics were summarized based on the FAS, which comprised all randomized patients who received the study application successfully.

Reporting Groups

	Description
Active group	receive the smart phone-based patient support tool
Control group	provided only the control application and not the smart phone-based patient support tool

Baseline Measures

	Active group	Control group	Total
Number of Participants [units: Participants]	431	423	854
Sex: Female, Male [units: ]
Female	161	154	315
Male	270	269	539
Age Continuous [units: Years] Mean ± Standard Deviation	54.7 ± 9.80	54.5 ± 9.51	54.6 ± 9.65
Race (NIH/OMB) [units: ]
American Indian or Alaska Native	0	0	0
Asian	431	423	854
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	0	0	0
More than one race	0	0	0
Unknown or Not Reported	0	0	0
Ethnicity (NIH/OMB) [units: ]
Hispanic or Latino	0	0	0
Not Hispanic or Latino	431	423	854
Unknown or Not Reported	0	0	0

Outcome Measures

1. Primary Outcome Measure: Duration of treatment [ Time Frame: limited to 169 days ]

Measure Type	Primary
Measure Name	Duration of treatment
Measure Description	The time from randomization to last patient reported visit (prior to the end-of-study visit) to a doctor to get a prescription for rosuvastatin plus the number of days of medicine provided in that last prescription.
Time Frame	limited to 169 days
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
Active group	receive the smart phone-based patient support tool
Control group	provided only the control application and not the smart phone-based patient support tool

Measured Values

	Active group	Control group
Number of Participants Analyzed [units:participants]	431	423
Duration of treatment [units: days] Mean (Standard Error)	156.7 (2.24)	146.0 (2.69)

Statistical Analysis 1 for Duration of treatment

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.0019

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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2. Secondary Outcome Measure: Percentage of fully adherent patients [ Time Frame: Up to 24 weeks ]

Measure Type	Secondary
Measure Name	Percentage of fully adherent patients
Measure Description	The number of patients who answered ‘Yes’ to Q4 of Rosuvastatin Adherence Questionnaire (RAQ) at all time points divided by the total number of randomized patients.
Time Frame	Up to 24 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
Active group	receive the smart phone-based patient support tool
Control group	provided only the control application and not the smart phone-based patient support tool

Measured Values

	Active group	Control group
Number of Participants Analyzed [units:participants]	431	423
Percentage of fully adherent patients [units: % of patients]	4.4	9.9

Statistical Analysis 1 for Percentage of fully adherent patients

Groups^[1]	All groups
Method^[3]	Chi-squared
P-Value^[4]	0.0017

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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3. Secondary Outcome Measure: Treatment adherence [ Time Frame: Up to 24 weeks ]

Measure Type	Secondary
Measure Name	Treatment adherence
Measure Description	The number of reported rosuvastatin tablets taken divided by the total number of days in the study.
Time Frame	Up to 24 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
Active group	receive the smart phone-based patient support tool
Control group	provided only the control application and not the smart phone-based patient support tool

Measured Values

	Active group	Control group
Number of Participants Analyzed [units:participants]	200	219
Treatment adherence [units: % adherence] Mean (Standard Deviation)	37.95 (32.916)	58.19 (36.257)

Statistical Analysis 1 for Treatment adherence

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-20.24
Standard Error of the mean	± 3.39
95% Confidence Interval	( -26.91 to -13.57 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
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4. Secondary Outcome Measure: Percent change in Low-Density Lipoprotein-Cholesterol (LDL-C) from baseline [ Time Frame: Baseline and Week 24 ]

Measure Type	Secondary
Measure Name	Percent change in Low-Density Lipoprotein-Cholesterol (LDL-C) from baseline
Measure Description	Low-Density Lipoprotein-Cholesterol (LDL-C) change from baseline at the Week 24 assessment for subjects who completed 24 weeks of treatment
Time Frame	Baseline and Week 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
Active group	receive the smart phone-based patient support tool
Control group	provided only the control application and not the smart phone-based patient support tool

Measured Values

	Active group	Control group
Number of Participants Analyzed [units:participants]	303	303
Percent change in Low-Density Lipoprotein-Cholesterol (LDL-C) from baseline [units: % change] Mean (Standard Error)	-21.09 (1.40)	-21.72 (1.40)

Statistical Analysis 1 for Percent change in Low-Density Lipoprotein-Cholesterol (LDL-C) from baseline

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.7514
Mean Difference (Final Values)^[5]	0.63
Standard Error of the mean	± 1.99
95% Confidence Interval	( -3.27 to 4.53 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	linear model including terms for randomized group and baseline LDL-C
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
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5. Post-Hoc Outcome Measure: Reported treatment adherence [ Time Frame: Up to 24 weeks ]

Measure Type	Post-Hoc
Measure Name	Reported treatment adherence
Measure Description	The number of reported rosuvastatin tablets taken divided by the total number of days reported during the treatment. This is eliminated any missing data from the calculation.
Time Frame	Up to 24 weeks
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
Active group	receive the smart phone-based patient support tool
Control group	provided only the control application and not the smart phone-based patient support tool

Measured Values

	Active group	Control group
Number of Participants Analyzed [units:participants]	200	219
Reported treatment adherence [units: % adherence] Mean (Standard Deviation)	94.63 (18.347)	96.01 (14.316)

Statistical Analysis 1 for Reported treatment adherence

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.3939
Mean Difference (Final Values)^[5]	-1.38
Standard Error of the mean	± 1.60
95% Confidence Interval	( -4.56 to 1.80 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Time Frame	177±7 days
Additional Description	This was an evaluation of the smart phone-based patient support tool, and rosuvastatin was not considered an investigational product for this study. There was no requirement to report AEs as part of the study, except the ones meeting the SAE criteria. Other [Not Including Serious] Adverse Events were not monitored/assessed.

Reporting Groups

	Description
Active group	receive the smart phone-based patient support tool
Control group	provided only the control application and not the smart phone-based patient support tool