Clinical trial NCT04807400: Study in Primary Care Evaluating Inclisiran Delivery Implementation + Enhanced Support
Official title: A Phase IIIb, Multicentre, Randomised Controlled Study to Evaluate the Implementation, Preference and Utility for Administration of Inclisiran Sodium in Participants With Atherosclerotic Cardiovascular Disease (ASCVD) or ASCVD-risk Equivalents and Elevated Low Density Lipoprotein Cholesterol (LDL-C) Using a Primary Care Models in the NHS.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atherosclerotic Cardiovascular Disease
Atherosclerotic Cardiovascular Disease Risk Equivelents
Elevated Low Density Lipoprotein Cholesterol
Keywords: Atherosclerotic Cardiovascular Disease
Atherosclerotic Cardiovascular Disease Risk Equivalents
Elevated Low Density Lipoprotein Cholesterol
ASCVD
LDL-C
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-03-19
Enrollment: 892
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage Change in LDL-C From Baseline to Day 270
timeFrame: Baseline, Day 270
Secondary outcomes:
measure: Number of Participants Interviewed for CFIR Analysis.
timeFrame: Day 270
measure: Patient Reported Outcomes: CSQ-8 Total Score After Treatment
timeFrame: Day 90
measure: Patient Reported Outcomes: CSQ-8 Total Score Between Inclisiran Arms
timeFrame: Day 90
measure: Change From Baseline to Day 90 in Total PAM Score
timeFrame: Baseline, Day 90
measure: Change From Baseline to Day 90 in Total PAM Score Between Inclisiran Arms
timeFrame: Baseline, Day 90
measure: Measures of Adherence to Cardiovascular Disease Self-management Using the Validated Patient Activation Measure (PAM) Questionnaire.
timeFrame: Baseline, Day 90
Other outcomes:
Locations:
city: Sale
country: United Kingdom
facility: Novartis Investigative Site
state: Cheshire
city: Altrincham
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Davyhulme
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Didsbury
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Northenden
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Sale
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Swinton
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Wythenshawe
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Wythenshawe
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Chadderton
country: United Kingdom
facility: Novartis Investigative Site
city: Cheadle Hulme
country: United Kingdom
facility: Novartis Investigative Site
city: Greater Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Lancashire
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: