Atherosclerotic Cardiovascular Disease, Atherosclerotic Cardiovascular Disease Risk Equivelents, Elevated Low Density Lipoprotein Cholesterol
Conditions
Keywords
Atherosclerotic Cardiovascular Disease, Atherosclerotic Cardiovascular Disease Risk Equivalents, Elevated Low Density Lipoprotein Cholesterol, ASCVD, LDL-C
Brief summary
The purpose of this study was to evaluate the implementation of inclisiran in a regional primary care setting in the UK Inclisiran, also known as KJX839, is a medication made to reduce the level of bad cholesterol (LDL-cholesterol) in the blood. Inclisiran works in a way that makes the liver produce less of a substance called 'PCSK9'. PCSK9 reduces the ability of the liver to remove LDL-cholesterol from the blood. By lowering the production of PCSK9, Inclisiran leads to more LDL-cholesterol being removed by the liver from the blood, thereby reducing LDL-cholesterol overall.
Detailed description
A phase IIIb, multicenter, randomized controlled study to evaluate the implementation, preference, and utility for administration of inclisiran sodium in participants on established lipid lowering medication or, have been recommended lipid lowering therapy by their healthcare provider but are unable to tolerate treatment, with elevated low density lipoprotein cholesterol (LDL-C) in a primary care population. This study was an implementation research study that utilized implementation science methodology and use of the electronic medical record (EMR). Using implementation science methodology, the study intended to assess the effect of 9 months treatment with inclisiran with/without behavioural support, compared to standard of care + behavioural support, on LDL-C reduction, total lipid profile, assessments of patient and healthcare professional (HCP) satisfaction, health-care resource utilization and healthcare service process evaluation. The primary focus of this study was implementation and 'transactability' - how to organize, deliver and maintain an innovative treatment for Atherosclerotic Cardiovascular Disease (ASCVD) in a primary care setting in a sustainable way. Patients taking part in the study were randomised to one of three groups: * Control + BS: Participants continued to receive their background lipid lowering therapy plus behavioural support. Subjects in treatment group 1 were referred to as the control group in this study * Inclisiran: Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model). * Inclisiran + BS: Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support. Participants who were randomized to Inclisiran or Inclisiran + BS received one injection of inclisiran on Day 1 and a second injection of inclisiran on Day 90. Participants in Control + BS and Inclisiran + BS received a monthly telephone call from a health advisor, providing support to enable participants to make positive behaviour changes to reduce their cardiovascular risk.
Interventions
DRUGInclisiran
Inclisiran Sodium 300mg on Day 1 and Day 90 by subcutaneous injection
BEHAVIORALBehavioural Support
Regular telephone based behavioural support programme delivered throughout the study period, as measured by point of care testing device.
DRUGBackground lipid lowering therapy
lipid-lowering therapy (such as a statin and/or ezetimibe) as background therapy
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Masking description
Open-Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent had to be obtained prior to participation in the study. 2. Patients on established lipid lowering medication or, have been recommended lipid lowering therapy by their health care provider but were unable to tolerate treatment. 3. A total cholesterol measurement at screening that was ≥4 mmol/L \[approximately 160 mg/dL\]. 4. Participants on lipid-lowering therapies had to be on a stable dose for ≥30 days before screening with no planned medication or dose change.
Exclusion criteria
1. Medical or surgical history that might limit the individual's ability to take study treatments for the duration of the study and/or put the participant at significant risk . 2. Current or planned renal dialysis or transplantation. 3. Acute coronary syndrome or stroke less than 4 weeks before the screening visit. 4. Coronary revascularization procedure planned within the next 6 months. 5. Women of child-bearing potential, unless they agree to abstinence or, if sexually active, agree to the use of effective methods of contraception during the study. 6. Women who are pregnant or breast-feeding. 7. Previous, current or planned treatment with a monoclonal antibody targeting PCSK9, or with a drug known to be contra-indicated with inclisiran. 8. Previous exposure to inclisiran or participation in a randomised study of inclisiran. 9. Current or previous participation in a clinical study with an unlicensed drug or device within 30 days or five half-lives of the screening visit, whichever is longer. 10. Participants who planed to move away from the geographical area where the study is being conducted during the study period. 11. A triglyceride measurement at screening that is greater than or equal to 4.52 mmol/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in LDL-C From Baseline to Day 270 | Baseline, Day 270 | Change in Low Density Lipoprotein Cholesterol (LDL-C) after 270 days of treatment in adults on established lipid lowering medication or who have been recommended lipid lowering therapy by their health care provider but are unable to tolerate treatment, regardless of treatment discontinuation for any reason and regardless of unforeseen change in the concomitant lipid lowering therapy. Multiple imputation is used to impute missing data using a washout model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Reported Outcomes: CSQ-8 Total Score After Treatment | Day 90 | The Client Satisfaction Questionnaire (CSQ)-8 is the standard self-administered CSQ scale containing 8 items that comprise the measurement of satisfaction with services and measurement of improvement of capacity to cope and change adaptively. Items include questions enquiring about respondents' opinions and conclusions about services they have received or are currently receiving. Response options differ from item to item, but all are based on a four-point scale. For the CSQ-8 version, scores range from 8 to 32, with higher values indicating higher satisfaction. |
| Patient Reported Outcomes: CSQ-8 Total Score Between Inclisiran Arms | Day 90 | The CSQ-8 is the standard self-administered CSQ scale containing 8 items that comprise the measurement of satisfaction with services and measurement of improvement of capacity to cope and change adaptively. Items include questions enquiring about respondents' opinions and conclusions about services they have received or are currently receiving. Response options differ from item to item, but all are based on a four-point scale. For the CSQ-8 version, scores range from 8 to 32, with higher values indicating higher satisfaction. This secondary outcome only analysed data of the two Inclisiran arms, by considering the Inclisiran only arm as the control group. The standard error for Least Square Mean could change because dropping a treatment arm affects the estimation of treatment effects and the variability of data. |
| Number of Participants Interviewed for CFIR Analysis. | Day 270 | To identify the need to support the implementation of inclisiran in the real world, a framework was drawn known as the Consolidated Framework for Implementation Research (CFIR). Patients who received inclisiran were interviewed to understand their experience with the program and to obtain a comprehensive understanding, with or without behavioural support. These patients were interviewed on various aspects of their experience related to their high cholesterol management, trial participation, inclisiran injections, attending appointments, and if applicable their experience with the behavioural support programme. These interviews were not set up in a way that allow numerical analysis. The process evaluation was conducted by Manchester University. |
| Change From Baseline to Day 90 in Total PAM Score Between Inclisiran Arms | Baseline, Day 90 | The Patient Activation Measure (PAM) questionnaire is a survey that assesses a person's underlying knowledge, skills and confidence integral to managing his or her own health and healthcare. This study used the 13-point PAM questionnaire, which consists of 13 statements. For each statement patients are required to say how much they either agree or disagree on a response scale of 1-5, where 1 represents strongly disagree, 4 represents strongly agree and 5 indicates that the statement is not applicable to them. Responses are used to generate a continuous score from 0 to 100 where higher scores indicate that the patient is more activated. This outcome only analysed data of the two inclisiran arms, by considering the Inclisiran only arm as the control group. In an ANCOVA model, the Least Squares Means and corresponding Standard Error could change because the removal of a treatment group affects the estimation of the treatment effects and the adjustment for the covariate(s). |
| Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Baseline, Day 90 | The Patient Activation Measure (PAM) questionnaire is a survey that assesses a person's underlying knowledge, skills and confidence integral to managing his or her own health and healthcare. This study used the 13-point PAM questionnaire, which consists of 13 statements relating to patients beliefs about health care, confidence in their management of health related tasks, and self-assessed knowledge of their condition. For each statement patients are required to say how much they either agree or disagree on a response scale of 1-5, where 1 represents strongly disagree, 4 represents strongly agree and 5 indicates that the statement is not applicable to them. Responses are used to generate a continuous score from 0 to 100. The continuous PAM scores are then categorised into 4 levels: Level 1 - disengaged and overwhelmed; Level 2 - become aware but still struggling; Level 3 - taking action; Level 4 - maintaining behaviors and pushing further. |
| Change From Baseline to Day 90 in Total PAM Score | Baseline, Day 90 | The Patient Activation Measure (PAM) questionnaire is a survey that assesses a person's underlying knowledge, skills and confidence integral to managing his or her own health and healthcare. This study used the 13-point PAM questionnaire, which consists of 13 statements relating to patients beliefs about health care, confidence in their management of health related tasks, and self-assessed knowledge of their condition. For each statement patients are required to say how much they either agree or disagree on a response scale of 1-5, where 1 represents strongly disagree, 4 represents strongly agree and 5 indicates that the statement is not applicable to them. A standardised spreadsheet in excel is used to score the PAM. Responses are used to generate a continuous score from 0 to 100 where higher scores indicate that the patient is more activated. |
Countries
United Kingdom
Participant flow
Recruitment details
The study was conducted at 17 primary care centres with a network of research ready General Practitioners across Greater Manchester, United Kingdom.
Pre-assignment details
Eligibility and recruitment to the study was optimized by using NorthWest EHealth's (NWEH) proven Feasibility Assessment and Recruitment System for Improving Trial Efficiency (FARSITE) for identification and recruitment at participating General Practitioner practices.
Participants by arm
| Arm | Count |
|---|---|
| Inclisiran Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model). | 297 |
| Inclisiran + BS Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support. | 297 |
| Control+ BS Participants continued to receive their background lipid lowering therapy plus behavioural support (BS). | 297 |
| Total | 891 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 3 |
| Overall Study | Death | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 8 | 6 | 6 |
| Overall Study | Mis-randomized | 1 | 0 | 0 |
| Overall Study | Non-Compliance With Study Drug | 0 | 4 | 1 |
| Overall Study | Participant Decision | 20 | 19 | 26 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 3 | 7 |
| Overall Study | Withdrawal by Subject | 13 | 9 | 20 |
Baseline characteristics
| Characteristic | Inclisiran | Inclisiran + BS | Control+ BS | Total |
|---|---|---|---|---|
| Age, Continuous | 66.0 Years STANDARD_DEVIATION 9.27 | 65.8 Years STANDARD_DEVIATION 9.71 | 66.7 Years STANDARD_DEVIATION 9.45 | 66.2 Years STANDARD_DEVIATION 9.47 |
| Race/Ethnicity, Customized Asian | 11 Participants | 3 Participants | 9 Participants | 23 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized Mixed | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 281 Participants | 289 Participants | 278 Participants | 848 Participants |
| Sex: Female, Male Female | 170 Participants | 174 Participants | 180 Participants | 524 Participants |
| Sex: Female, Male Male | 127 Participants | 123 Participants | 117 Participants | 367 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 273 | 0 / 281 | 0 / 290 | 2 / 844 |
| other Total, other adverse events | 3 / 273 | 2 / 281 | 0 / 290 | 5 / 844 |
| serious Total, serious adverse events | 24 / 273 | 36 / 281 | 28 / 290 | 88 / 844 |
Outcome results
Primary
Percentage Change in LDL-C From Baseline to Day 270
Change in Low Density Lipoprotein Cholesterol (LDL-C) after 270 days of treatment in adults on established lipid lowering medication or who have been recommended lipid lowering therapy by their health care provider but are unable to tolerate treatment, regardless of treatment discontinuation for any reason and regardless of unforeseen change in the concomitant lipid lowering therapy. Multiple imputation is used to impute missing data using a washout model.
Time frame: Baseline, Day 270
Population: Full analysis set. The Full Analysis Set (FAS) comprised of all randomized participants except for those mis-randomized participants who did not receive study drug. Only participants with LDL-C values at both, baseline and Day 270, were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Inclisiran | Percentage Change in LDL-C From Baseline to Day 270 | -37.3 percent change from baseline in LDL-C | Standard Error 2.29 |
| Inclisiran + BS | Percentage Change in LDL-C From Baseline to Day 270 | -37.6 percent change from baseline in LDL-C | Standard Error 2.33 |
| Control+ BS | Percentage Change in LDL-C From Baseline to Day 270 | -5.4 percent change from baseline in LDL-C | Standard Error 2.34 |
p-value: <0.00195% CI: [-37.91, -25.77]ANCOVA
p-value: <0.00195% CI: [-38.35, -25.94]ANCOVA
Secondary
Change From Baseline to Day 90 in Total PAM Score
The Patient Activation Measure (PAM) questionnaire is a survey that assesses a person's underlying knowledge, skills and confidence integral to managing his or her own health and healthcare. This study used the 13-point PAM questionnaire, which consists of 13 statements relating to patients beliefs about health care, confidence in their management of health related tasks, and self-assessed knowledge of their condition. For each statement patients are required to say how much they either agree or disagree on a response scale of 1-5, where 1 represents strongly disagree, 4 represents strongly agree and 5 indicates that the statement is not applicable to them. A standardised spreadsheet in excel is used to score the PAM. Responses are used to generate a continuous score from 0 to 100 where higher scores indicate that the patient is more activated.
Time frame: Baseline, Day 90
Population: Full analysis set: The Full Analysis Set (FAS) comprised of all randomized participants except for those mis-randomized participants who did not receive study drug. Only participants with PAM assessment at both, Baseline and Day 90, were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Inclisiran | Change From Baseline to Day 90 in Total PAM Score | 2.4 score on a scale | Standard Error 1.18 |
| Inclisiran + BS | Change From Baseline to Day 90 in Total PAM Score | 2.7 score on a scale | Standard Error 1.14 |
| Control+ BS | Change From Baseline to Day 90 in Total PAM Score | 1.4 score on a scale | Standard Error 2.01 |
p-value: 0.675995% CI: [-3.62, 5.58]ANCOVA
p-value: 0.575695% CI: [-3.25, 5.84]ANCOVA
Secondary
Change From Baseline to Day 90 in Total PAM Score Between Inclisiran Arms
The Patient Activation Measure (PAM) questionnaire is a survey that assesses a person's underlying knowledge, skills and confidence integral to managing his or her own health and healthcare. This study used the 13-point PAM questionnaire, which consists of 13 statements. For each statement patients are required to say how much they either agree or disagree on a response scale of 1-5, where 1 represents strongly disagree, 4 represents strongly agree and 5 indicates that the statement is not applicable to them. Responses are used to generate a continuous score from 0 to 100 where higher scores indicate that the patient is more activated. This outcome only analysed data of the two inclisiran arms, by considering the Inclisiran only arm as the control group. In an ANCOVA model, the Least Squares Means and corresponding Standard Error could change because the removal of a treatment group affects the estimation of the treatment effects and the adjustment for the covariate(s).
Time frame: Baseline, Day 90
Population: Full analysis set: The Full Analysis Set (FAS) comprised of all randomized participants except for those mis-randomized participants who did not receive study drug. Only participants assigned to inlcisiran with PAM assessment at Day 90, were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Inclisiran | Change From Baseline to Day 90 in Total PAM Score Between Inclisiran Arms | 2.6 score on a scale | Standard Error 1.17 |
| Inclisiran + BS | Change From Baseline to Day 90 in Total PAM Score Between Inclisiran Arms | 2.3 score on a scale | Standard Error 1.21 |
p-value: 0.85895% CI: [-3.02, 3.62]ANCOVA
Secondary
Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire.
The Patient Activation Measure (PAM) questionnaire is a survey that assesses a person's underlying knowledge, skills and confidence integral to managing his or her own health and healthcare. This study used the 13-point PAM questionnaire, which consists of 13 statements relating to patients beliefs about health care, confidence in their management of health related tasks, and self-assessed knowledge of their condition. For each statement patients are required to say how much they either agree or disagree on a response scale of 1-5, where 1 represents strongly disagree, 4 represents strongly agree and 5 indicates that the statement is not applicable to them. Responses are used to generate a continuous score from 0 to 100. The continuous PAM scores are then categorised into 4 levels: Level 1 - disengaged and overwhelmed; Level 2 - become aware but still struggling; Level 3 - taking action; Level 4 - maintaining behaviors and pushing further.
Time frame: Baseline, Day 90
Population: Full analysis set: The Full Analysis Set (FAS) comprised of all randomized participants except for those mis-randomized participants who did not receive study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 1 (Disengaged and overwhelmed) at Baseline | 13 Participants |
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 1 (Disengaged and overwhelmed) at Day 90 | 9 Participants |
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 3 (Taking action) at Day 90 | 63 Participants |
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 2 (Become aware but still struggling) at Baseline | 47 Participants |
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 3 (Taking action) at Baseline | 61 Participants |
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 4 (Maintaining behaviors and pushing further) at Baseline | 48 Participants |
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Missing PAM scores at baseline | 128 Participants |
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 2 (Become aware but still struggling) Day 90 | 37 Participants |
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 4 (Maintaining behaviors and pushing further) at Day 90 | 56 Participants |
| Inclisiran | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Missing PAM scores at Day 90 | 132 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 3 (Taking action) at Baseline | 75 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 4 (Maintaining behaviors and pushing further) at Day 90 | 47 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 4 (Maintaining behaviors and pushing further) at Baseline | 44 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Missing PAM scores at baseline | 108 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 1 (Disengaged and overwhelmed) at Day 90 | 8 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 2 (Become aware but still struggling) Day 90 | 38 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 3 (Taking action) at Day 90 | 64 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 1 (Disengaged and overwhelmed) at Baseline | 20 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 2 (Become aware but still struggling) at Baseline | 50 Participants |
| Inclisiran + BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Missing PAM scores at Day 90 | 140 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Missing PAM scores at Day 90 | 189 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 3 (Taking action) at Baseline | 36 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 2 (Become aware but still struggling) Day 90 | 23 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 1 (Disengaged and overwhelmed) at Baseline | 7 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 4 (Maintaining behaviors and pushing further) at Baseline | 21 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 4 (Maintaining behaviors and pushing further) at Day 90 | 33 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 3 (Taking action) at Day 90 | 46 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Missing PAM scores at baseline | 218 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 2 (Become aware but still struggling) at Baseline | 15 Participants |
| Control+ BS | Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. | Level 1 (Disengaged and overwhelmed) at Day 90 | 6 Participants |
Secondary
Number of Participants Interviewed for CFIR Analysis.
To identify the need to support the implementation of inclisiran in the real world, a framework was drawn known as the Consolidated Framework for Implementation Research (CFIR). Patients who received inclisiran were interviewed to understand their experience with the program and to obtain a comprehensive understanding, with or without behavioural support. These patients were interviewed on various aspects of their experience related to their high cholesterol management, trial participation, inclisiran injections, attending appointments, and if applicable their experience with the behavioural support programme. These interviews were not set up in a way that allow numerical analysis. The process evaluation was conducted by Manchester University.
Time frame: Day 270
Population: All patients randomized to inclisiran
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inclisiran | Number of Participants Interviewed for CFIR Analysis. | 28 Participants |
| Inclisiran + BS | Number of Participants Interviewed for CFIR Analysis. | 28 Participants |
Secondary
Patient Reported Outcomes: CSQ-8 Total Score After Treatment
The Client Satisfaction Questionnaire (CSQ)-8 is the standard self-administered CSQ scale containing 8 items that comprise the measurement of satisfaction with services and measurement of improvement of capacity to cope and change adaptively. Items include questions enquiring about respondents' opinions and conclusions about services they have received or are currently receiving. Response options differ from item to item, but all are based on a four-point scale. For the CSQ-8 version, scores range from 8 to 32, with higher values indicating higher satisfaction.
Time frame: Day 90
Population: Full analysis set: The Full Analysis Set (FAS) comprised of all randomized participants except for those mis-randomized participants who did not receive study drug. Only participants with CSQ-8 assessment Day 90, were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Inclisiran | Patient Reported Outcomes: CSQ-8 Total Score After Treatment | 30.1 score on a scale | Standard Error 0.24 |
| Inclisiran + BS | Patient Reported Outcomes: CSQ-8 Total Score After Treatment | 30.1 score on a scale | Standard Error 0.24 |
| Control+ BS | Patient Reported Outcomes: CSQ-8 Total Score After Treatment | 28.7 score on a scale | Standard Error 0.3 |
p-value: <0.00195% CI: [0.62, 2.13]ANOVA
p-value: <0.00195% CI: [0.6, 2.1]ANOVA
Secondary
Patient Reported Outcomes: CSQ-8 Total Score Between Inclisiran Arms
The CSQ-8 is the standard self-administered CSQ scale containing 8 items that comprise the measurement of satisfaction with services and measurement of improvement of capacity to cope and change adaptively. Items include questions enquiring about respondents' opinions and conclusions about services they have received or are currently receiving. Response options differ from item to item, but all are based on a four-point scale. For the CSQ-8 version, scores range from 8 to 32, with higher values indicating higher satisfaction. This secondary outcome only analysed data of the two Inclisiran arms, by considering the Inclisiran only arm as the control group. The standard error for Least Square Mean could change because dropping a treatment arm affects the estimation of treatment effects and the variability of data.
Time frame: Day 90
Population: Full analysis set: The Full Analysis Set (FAS) comprised of all randomized participants except for those mis-randomized participants who did not receive study drug. Only participants assigned to inclisiran with CSQ-8 assessment Day 90, were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Inclisiran | Patient Reported Outcomes: CSQ-8 Total Score Between Inclisiran Arms | 30.1 score on a scale | Standard Error 0.23 |
| Inclisiran + BS | Patient Reported Outcomes: CSQ-8 Total Score Between Inclisiran Arms | 30.1 score on a scale | Standard Error 0.23 |
p-value: 0.934795% CI: [-0.67, 0.61]ANOVA