Percutaneous Coronary Intervention, Peripheral Endovascular Intervention
Conditions
Keywords
inclisiran, Coronary Artery Disease, hypercholesterolemia, Cardiovascular Disease, Percutaneous Endovascular Intervention, Percutaneous Coronary Intervention, PCSK9
Brief summary
V-INTERVENTION will evaluate the effectiveness of inclisiran in preventing major cardiovascular and limb events in patients receiving percutaneous coronary or peripheral arterial revascularization. Inclisiran is a subcutaneous, twice-yearly injection that is FDA-approved as an adjunct with statin therapy and on the market to lower LDL-C in high-risk populations.
Detailed description
CKJX839D1US04R is a pragmatic, randomized, double-blind, parallel group, placebo-controlled, multicenter, event-driven study evaluating inclisiran sodium 300 mg subcutaneous administered on Day 1, Month 3 (Day 90), and every 6 months thereafter in participants presenting for elective or urgent percutaneous coronary or peripheral endovascular intervention (PCI or PVI). At the time of a successful revascularization procedure or up to 14 days following the procedure, participants will be randomized and administered the first dose of inclisiran or corresponding placebo in a 1:1 fashion, stratified by the type of index arterial revascularization procedure, either coronary (i.e., PCI) or lower extremity (i.e., PV). The enrollment population will be representative of typical patients in the US with atherosclerotic cardiovascular disease, either coronary artery disease (CAD) or peripheral artery disease (PAD), and the trial endpoints are designed to be scientifically relevant and clinically meaningful to patients, clinicians, and other persons involved in the care of cardiovascular patients. The trial is designed to also understand how inclisiran therapy can be implemented in real-world clinical practice settings. The expected enrollment of the trial is approximately 6,000 participants, randomized in a 1:1 fashion to receive inclisiran or placebo, within 14 days of successful percutaneous coronary or lower extremity peripheral endovascular intervention for symptomatic atherosclerotic cardiovascular disease (ASCVD). Inclisiran sodium or corresponding placebo will be administered by s.c. injection to participants presenting for percutaneous coronary or peripheral endovascular intervention, in addition to usual care according to their individual medical history. All participants randomized to the treatment arm will receive inclisiran in addition to usual care per their regular physician direction, and those participants randomized to placebo will receive matching placebo, as well as usual care treatment, according to their treating physician. Study duration is determined by event accrual consistent with the event-driven design, i.e., when approximately 2380 primary composite events have occurred and at least 50% of participants have at least 36 months of follow-up. Assuming 18 months of recruitment at a uniform rate, the last patients enrolled will have about 27 months of follow-up. Therefore, study duration should be approximately 4 years. The study is event-driven, and thus, all participants will be treated (or followed in the case of permanent discontinuation of study drug) until the End of Study visit. As such, the planned duration of treatment cannot be stipulated for an individual participant. The estimated maximum treatment period for an individual participant is approximately 45 months, and the mean treatment duration is expected to be approximately 36 months.
Interventions
300 mg (equivalent to 284 mg inclisiran) in 1.5 mL subcutaneous injection at Day 0; Day 90; \& every 6 months thereafter
DRUGNormal Saline (Placebo)
Normal saline placebo subcutaneous injection given at Day 0, Day 90; \& every 6 months thereafter
Sponsors
Duke University
Novartis Pharmaceuticals
Colorado Prevention Center
Mount Sinai Hospital, New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent must be obtained prior to participation in the study. * Males or females ≥ 18 years of age * Within 14 days of a successful percutaneous coronary intervention (PCI) or peripheral endovascular intervention (PVI) for symptomatic CAD or lower extremity PAD * Patients undergoing planned staged interventions are eligible for randomization only after the last planned intervention
Exclusion criteria
* Planned future PCI or PVI * Current or planned use of an open-label PCSK9 inhibitor during the study * Any prior treatment with inclisiran * Active or planned participation in another clinical study involving investigational drugs or devices during the study * Any serious liver disease, metabolic disease, neoplasm, end-stage kidney disease, or other condition in the opinion of the investigator that would inhibit trial participation or confound trial results * Any other reason why, in the opinion of the investigator, the participant would not be suitable for study participation including safety considerations and the ability to adhere to protocol activities * Patients taking prohibited therapies as listed in Section 6.6.3 * Pregnant or breast-feeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total number of major adverse cardiovascular events (MACE) after coronary or peripheral endovascular revascularization | From randomization to first occurrence of MACE (up to approximately 4 years) | MACEs include CHD death, non-fatal MI, ischemic stroke, ALI, major (above the ankle) amputation of vascular etiology, clinically driven coronary and limb revascularization. |
| Total number of major adverse limb events (MALE) after endovascular revascularization | From randomization to first occurrence of MALE (up to approximately 4 years) | MALEs consist of ALI, major amputation of vascular etiology, clinically driven lower extremity peripheral revascularization. |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with cardiovascular (CV) death | From randomization to CV death (up to approximately 4 years) |
| Number of participants with all cause death | From randomization to all cause death (up to approximately 4 years) |
| Number of participants with venous thromboembolic events (VTE) | From randomization to first VTE (up to approximately 4 years) |
Countries
United States
Contacts
CONTACTRobin Barron-Nelson, RN, MSN
CONTACTJen Holt
PRINCIPAL_INVESTIGATORSchuyler Jones, MD
Duke Clinical Research Institute
PRINCIPAL_INVESTIGATORMarc Bonaca, MD
Colorado Prevention Center
STUDY_CHAIRRoxana Mehran, MD
Mt Sinai
STUDY_CHAIRManesh Patel, MD
Duke University
Outcome results
None listed