Trial Outcomes & Findings for Study in Primary Care Evaluating Inclisiran Delivery Implementation + Enhanced Support (NCT NCT04807400)

Last Updated: 2024-10-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

892 participants

Primary outcome timeframe

Baseline, Day 270

Results posted on

2024-10-09

Participant Flow

The study was conducted at 17 primary care centres with a network of research ready General Practitioners across Greater Manchester, United Kingdom.

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.

Participant milestones

Participant milestones
Measure	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.	Control+ BS Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).
Overall Study STARTED	298	297	297
Overall Study Full Analysis Set	297	297	297
Overall Study Safety Set	273	281	290
Overall Study COMPLETED	248	252	234
Overall Study NOT COMPLETED	50	45	63

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Control+ BS Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).
Overall Study Adverse Event	2	3	3
Overall Study Death	2	0	0
Overall Study Lost to Follow-up	8	6	6
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
Overall Study Mis-randomized	1	0	0

Baseline Characteristics

Study in Primary Care Evaluating Inclisiran Delivery Implementation + Enhanced Support

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inclisiran n=297 Participants Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).	Inclisiran + BS n=297 Participants Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.	Control+ BS n=297 Participants Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).	Total n=891 Participants Total of all reporting groups
Age, Continuous	66.0 Years STANDARD_DEVIATION 9.27 • n=5 Participants	65.8 Years STANDARD_DEVIATION 9.71 • n=7 Participants	66.7 Years STANDARD_DEVIATION 9.45 • n=5 Participants	66.2 Years STANDARD_DEVIATION 9.47 • n=4 Participants
Sex: Female, Male Female	170 Participants n=5 Participants	174 Participants n=7 Participants	180 Participants n=5 Participants	524 Participants n=4 Participants
Sex: Female, Male Male	127 Participants n=5 Participants	123 Participants n=7 Participants	117 Participants n=5 Participants	367 Participants n=4 Participants
Race/Ethnicity, Customized Asian	11 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants	23 Participants n=4 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Mixed	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized White	281 Participants n=5 Participants	289 Participants n=7 Participants	278 Participants n=5 Participants	848 Participants n=4 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inclisiran n=294 Participants Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).	Inclisiran + BS n=295 Participants Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.	Control+ BS n=293 Participants Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).
Percentage Change in LDL-C From Baseline to Day 270	-37.3 percent change from baseline in LDL-C Standard Error 2.29	-37.6 percent change from baseline in LDL-C Standard Error 2.33	-5.4 percent change from baseline in LDL-C Standard Error 2.34

SECONDARY outcome

Timeframe: Day 270

Population: All patients randomized to inclisiran

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.

Outcome measures

Outcome measures
Measure	Inclisiran n=297 Participants Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).	Inclisiran + BS n=297 Participants Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.	Control+ BS Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).
Number of Participants Interviewed for CFIR Analysis.	28 Participants	28 Participants	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Inclisiran n=160 Participants Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).	Inclisiran + BS n=163 Participants Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.	Control+ BS n=105 Participants Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).
Patient Reported Outcomes: CSQ-8 Total Score After Treatment	30.1 score on a scale Standard Error 0.24	30.1 score on a scale Standard Error 0.24	28.7 score on a scale Standard Error 0.30

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Inclisiran n=163 Participants Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).	Inclisiran + BS n=160 Participants Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.	Control+ BS Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).
Patient Reported Outcomes: CSQ-8 Total Score Between Inclisiran Arms	30.1 score on a scale Standard Error 0.23	30.1 score on a scale Standard Error 0.23	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Inclisiran n=108 Participants Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).	Inclisiran + BS n=115 Participants Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.	Control+ BS n=37 Participants Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).
Change From Baseline to Day 90 in Total PAM Score	2.4 score on a scale Standard Error 1.18	2.7 score on a scale Standard Error 1.14	1.4 score on a scale Standard Error 2.01

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Inclisiran n=115 Participants Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).	Inclisiran + BS n=108 Participants Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.	Control+ BS Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).
Change From Baseline to Day 90 in Total PAM Score Between Inclisiran Arms	2.6 score on a scale Standard Error 1.17	2.3 score on a scale Standard Error 1.21	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Inclisiran n=297 Participants Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).	Inclisiran + BS n=297 Participants Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.	Control+ BS n=297 Participants Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).
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	20 Participants	7 Participants
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	50 Participants	15 Participants
Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. Level 3 (Taking action) at Baseline	61 Participants	75 Participants	36 Participants
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	44 Participants	21 Participants
Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. Missing PAM scores at baseline	128 Participants	108 Participants	218 Participants
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	8 Participants	6 Participants
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	38 Participants	23 Participants
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	64 Participants	46 Participants
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	47 Participants	33 Participants
Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire. Missing PAM scores at Day 90	132 Participants	140 Participants	189 Participants

Adverse Events

Inclisiran

Serious events: 24 serious events

Other events: 3 other events

Deaths: 2 deaths

Inclisiran + BS

Serious events: 36 serious events

Other events: 2 other events

Deaths: 0 deaths

Control + BS

Serious events: 28 serious events

Other events: 0 other events

Deaths: 0 deaths

Total

Serious events: 88 serious events

Other events: 5 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Inclisiran n=273 participants at risk Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).	Inclisiran + BS n=281 participants at risk Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.	Control + BS n=290 participants at risk Participants continued to receive their background lipid lowering therapy plus behavioural support (BS).	Total n=844 participants at risk Total
General disorders Injection site rash	0.37% 1/273 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/281 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/290 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.12% 1/844 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.
Musculoskeletal and connective tissue disorders Back pain	0.37% 1/273 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/281 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/290 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.12% 1/844 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.
Musculoskeletal and connective tissue disorders Muscle spasms	0.37% 1/273 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/281 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/290 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.12% 1/844 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.
Musculoskeletal and connective tissue disorders Pain in extremity	0.37% 1/273 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/281 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/290 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.12% 1/844 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.
Nervous system disorders Dizziness	0.00% 0/273 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.36% 1/281 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/290 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.12% 1/844 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.
Skin and subcutaneous tissue disorders Rash	0.00% 0/273 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.36% 1/281 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.00% 0/290 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.	0.12% 1/844 • Adverse events were reported from first dose of study treatment until end of study visit plus 30 days post treatment, up to a maximum duration of 300 days. Any sign or symptom that occurs during the conduct of the trial and the safety follow-up.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER