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A Randomized Study to Evaluate the Effect of an "Inclisiran First" Implementation Strategy Compared to Usual Care in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C Despite Receiving Maximally Tolerated Statin Therapy (VICTORION-INITIATE) (V-INITIATE)

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ClinicalTrials.gov Identifier: NCT04929249
Recruitment Status : Recruiting
First Posted : June 18, 2021
Last Update Posted : June 6, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to assess the effectiveness of an "inclisiran first" implementation strategy (addition of inclisiran to maximally tolerated statin therapy immediately upon failure to achieve acceptable LDL-C with maximally tolerated statin therapy alone) compared to usual care in an ASCVD population.

Condition or disease Intervention/treatment Phase
Atherosclerotic Cardiovascular Disease Drug: Inclisiran Phase 3

Detailed Description:

The study design will be a randomized, two-arm, parallel-group, open-label, multicenter, clinical trial comparing an "inclisiran first" implementation strategy to usual care in approximately 444 participants (1:1 randomization) with established ASCVD and elevated LDL-C (or non-HDL-C) despite treatment with maximally tolerated statin therapy.

The study will include male and female participants ≥18 years of age with a history of ASCVD (coronary heart disease, ischemic cerebrovascular disease or peripheral arterial disease) who have elevated LDL-C (≥70 mg/dL) or non-HDL-C (≥100 mg/dL) despite being treated with maximally tolerated statin therapy. A total of approximately 444 participants will be randomized to the "inclisiran first" implementation strategy or usual care in a 1:1 ratio at approximately 40 US sites.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 444 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomized, two-arm, parallel-group, open-label, multicenter clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Open-label Trial Comparing the Effectiveness of an "Inclisiran First" Implementation Strategy to Usual Care on LDL Cholesterol (LDL-C) in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C (≥70 mg/dL) Despite Receiving Maximally Tolerated Statin Therapy (VICTORION-INITIATE)
Actual Study Start Date : June 25, 2021
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Inclisiran First
Inclisiran + usual care
Drug: Inclisiran
284 mg liquid in prefilled syringe (PFS), 1.5 ml inclisiran sodium (300 mg)
Other Name: Inclisiran First

No Intervention: Usual Care
Usual care



Primary Outcome Measures :
  1. Percent change from baseline in LDL-C [ Time Frame: Day 330 ]
    To assess the effect on LDL-C of an "inclisiran-first" implementation strategy compared to usual care at Day 330 in participants with ASCVD and an LDL-C ≥70 mg/dL despite maximally tolerated statin therapy

  2. Discontinuation of statin therapy (i.e., no statin use ≥ 30 days before the end-of-study visit) (yes, no) [ Time Frame: Day 330 ]
    To assess the non-inferiority of an "inclisiran first" implementation strategy compared to usual care on discontinuation of background statin therapy at Day 330


Secondary Outcome Measures :
  1. Absolute change from baseline in LDL-C [ Time Frame: Day 330 ]
    To assess the absolute change in LDL-C of an "inclisiran first" implementation strategy compared to usual care at Day 330

  2. Average percent change from baseline in LDL-C levels to each post-baseline visit [ Time Frame: Day 330 ]
    To assess the average percent change in LDL-C of an "inclisiran first" implementation strategy compared to usual care to each post-baseline visit

  3. Average absolute change from baseline in LDL-C to each post-baseline visit [ Time Frame: Day 330 ]
    To assess the average absolute change in LDL-C of an "inclisiran first" implementation strategy compared to usual care to each post-baseline visit

  4. Achieving ≥ 50% reduction from baseline in LDL-C (yes, no) [ Time Frame: Day 330 ]
    To assess the proportion of participants reaching pre-specified LDL-C targets among those receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  5. Achieving LDL-C < 100 mg/dL (among the subset of participants with LDL-C >100 mg/dL at baseline) (yes, no) [ Time Frame: Day 330 ]
    To assess the proportion of participants reaching pre-specified LDL-C targets among those receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  6. Achieving LDL-C < 70 mg/dL (yes, no) [ Time Frame: Day 330 ]
    To assess the proportion of participants reaching pre-specified LDL-C targets among those receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  7. Achieving LDL-C < 55 mg/dL (yes, no) [ Time Frame: Day 330 ]
    To assess the proportion of participants reaching pre-specified LDL-C targets among those receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  8. Percent change and absolute change from baseline in apoB [ Time Frame: Day 330 ]
    To assess apoB in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  9. Percent change and absolute change from baseline in non-HDL-C [ Time Frame: Day 330 ]
    To assess non-HDL-C in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  10. Percent change and absolute change from baseline in VLDL-C [ Time Frame: Day 330 ]
    To assess VLDL-C in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  11. Percent change and absolute change from baseline in total cholesterol [ Time Frame: Day 330 ]
    To assess total cholesterol in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  12. Percent change and absolute change from baseline in Lp(a) [ Time Frame: Day 330 ]
    To assess Lp(a) in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  13. Percent change and absolute change from baseline in HDL-C [ Time Frame: Day 330 ]
    To assess HDL-C in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  14. Percent change and absolute change from baseline in triglycerides [ Time Frame: Day 330 ]
    To assess triglycerides in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  15. Intensity of lipid lowering therapy (decrease in dose, no change in dose, increase in dose) [ Time Frame: Day 330 ]
    To assess changes in background lipid-lowering therapy in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  16. Proportion of days covered (total number of days on either statin, ezetimibe, bempedoic acid or PCSK9 inhibiting monoclonal antibody therapies divided by total number of study days) [ Time Frame: Day 330 ]
    To assess adherence to background lipid-lowering therapy in participants receiving an "inclisiran first" implementation strategy compared to usual care at Day 330

  17. LDL-C measures of variability (standard deviation, coefficient of variation) [ Time Frame: Day 90 to Day 330 ]
    To assess visit-to-visit LDL-C variability from Day 90 until Day 330



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

  1. Signed informed consent must be obtained prior to participation in the study
  2. Males and females ≥18 years of age
  3. History of ASCVD, documented by hospital records, claims data and/or prior laboratory/imaging assessments
  4. Serum LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL
  5. Fasting triglyceride <5.65 mmol/L (<500 mg/dL) at screening
  6. Calculated glomerular filtration rate >30 mL/min by estimated glomerular filtration rate (eGFR) using standardized local clinical methodology
  7. Participants should be on maximally tolerated statin therapy, as determined by the investigator, with no immediate plans to modify lipid lowering therapies. Statin intolerant patients are eligible if they had documented side effects on at least 2 different statins, including one at the lowest standard dose
  8. Participants must be willing and able to give informed consent before initiation of any study related procedures and willing to comply with all required study procedures

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study.

  1. Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the participant at significant risk (according to investigator's [or delegate] judgment) if he/she participates in the clinical study
  2. An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results
  3. New York Heart Association (NYHA) class III or IV heart failure or last known left ventricular ejection fraction <30%
  4. Significant cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or via ablation at the time of screening
  5. Major adverse cardiovascular event within 6 months prior to randomization
  6. Uncontrolled severe hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite antihypertensive therapy
  7. Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years
  8. History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the two years prior to randomization
  9. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of investigational drug. Basic contraception methods include:

    1. Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
    2. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
    3. Male sterilization (at least 6 m prior to screening). For female participants in the study, the vasectomized male partner should be the sole partner for that participant
    4. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps)
    5. Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.

    Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

  10. Known history of alcohol and/or drug abuse within the last 5 years (occasional casual users of illicit drugs in the opinion of the investigators are not excluded)
  11. Treatment with other investigational products or devices within 30 days or five half-lives of the screening visit, whichever is longer
  12. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
  13. Planned use of other investigational products or devices during the course of the study
  14. Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:

    1. Participants who are unable to communicate or to cooperate with the investigator
    2. Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including participants whose cooperation is doubtful due to drug abuse or alcohol dependency)
    3. Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study - including potential participants who indicate that their participation is contingent on receiving inclisiran)
    4. Have any medical or surgical condition, which in the opinion of the investigator would put the participant at increased risk from participating in the study
    5. Persons directly involved in the conduct of the study
  15. Previous or current treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9 or ezetimibe
  16. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or alanine aminotransferase (ALT) elevation >3x ULN, aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation >2x ULN (except patients with Gilbert's syndrome) at screening confirmed by a repeat measurement at least one week apart

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04929249


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Arkansas
Novartis Investigative Site Recruiting
Little Rock, Arkansas, United States, 72205
United States, Connecticut
Novartis Investigative Site Recruiting
Greenwich, Connecticut, United States, 06830
Novartis Investigative Site Recruiting
Stamford, Connecticut, United States, 06905
United States, Florida
Novartis Investigative Site Recruiting
Fort Lauderdale, Florida, United States, 33312
Novartis Investigative Site Recruiting
Hialeah, Florida, United States, 33012
Novartis Investigative Site Recruiting
Jacksonville, Florida, United States, 32209
Novartis Investigative Site Recruiting
Jacksonville, Florida, United States, 32216
United States, Illinois
Novartis Investigative Site Recruiting
Jerseyville, Illinois, United States, 62052
Novartis Investigative Site Recruiting
Oak Brook, Illinois, United States, 60523
Novartis Investigative Site Recruiting
Winfield, Illinois, United States, 60190
United States, Indiana
Novartis Investigative Site Recruiting
Indianapolis, Indiana, United States, 46202
United States, Iowa
Novartis Investigative Site Recruiting
Davenport, Iowa, United States, 52801
United States, Louisiana
Novartis Investigative Site Recruiting
Alexandria, Louisiana, United States, 71301
United States, Maryland
Novartis Investigative Site Recruiting
Baltimore, Maryland, United States, 21218
Novartis Investigative Site Recruiting
Baltimore, Maryland, United States, 21239
United States, Nebraska
Novartis Investigative Site Recruiting
Lincoln, Nebraska, United States, 68506
United States, New Jersey
Novartis Investigative Site Recruiting
Elmer, New Jersey, United States, 08318
Novartis Investigative Site Recruiting
Linden, New Jersey, United States, 07036
United States, Pennsylvania
Novartis Investigative Site Recruiting
Camp Hill, Pennsylvania, United States, 17011
Novartis Investigative Site Recruiting
Newport, Pennsylvania, United States, 17074
Novartis Investigative Site Recruiting
Yardley, Pennsylvania, United States, 19067
United States, Tennessee
Novartis Investigative Site Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Novartis Investigative Site Recruiting
Cypress, Texas, United States, 77429
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77024
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77036
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77070
Novartis Investigative Site Recruiting
Webster, Texas, United States, 77598
United States, Virginia
Novartis Investigative Site Recruiting
Lynchburg, Virginia, United States, 24501
Novartis Investigative Site Recruiting
Richmond, Virginia, United States, 23294
United States, West Virginia
Novartis Investigative Site Recruiting
Morgantown, West Virginia, United States, 26501
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04929249    
Other Study ID Numbers: CKJX839A1US02
First Posted: June 18, 2021    Key Record Dates
Last Update Posted: June 6, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Hyperlipidemia
Secondary Cardiovascular Prevention
Atherosclerotic Cardiovascular Disease (ASCVD)
Hypercholesterolemia
Lipid lowering therapies
Inclisiran
Additional relevant MeSH terms:
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Cardiovascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases