Clinical trial

Efficacy and Safety of Pitavastatin and PCSK9 Inhibitors in Liver Transplant Patients

Name

2.0_17.03.22

Description

To study the efficacy and safety of pitavastatin and PCSK9 inhibitors in liver transplant patients on ongoing immunosuppressive therapy.

Trial arms

Trial start

2021-10-01

Estimated PCD

2024-06-30

Trial end

2025-01-31

Status

Recruiting

Phase

Early phase I

Treatment

Pitavastatin

First phase (6 months): Patients will be randomized 1:1 into 2 groups: 1. pitavastatin monotherapy 2. monotherapy with a PCSK9 inhibitor (evolocumab 140 mg or alirocumab 150 mg once every 2 weeks subcutaneously) In the group of Pitavastatin: Pitavastatin at visit 0 will be prescribed at a dose of 2 mg, after 1 month in the absence of side effects against the background of ongoing therapy, the dose will be increased to 4 mg. The lipid profile and safety of the therapy will be assessed in 1, 3 and 6 months after the start of the therapy. When triglyceride levels rise above 5.7 mmol/l in two consecutive analyzes, the addition of fenofibrate may be considered. Second phase (6 months): If the target level of LDL-C is not achieved during monotherapy with pitavastatin, the patient will be asked to continue treatment with combined lipid-lowering therapy (pitavastatin + PCSK9 inhibitor). There will be visits on the 7th, 9th and 12th months.

Arms:

pitavastatin

PCSK9 inhibitor

First phase (6 months): Patients will be randomized 1:1 into 2 groups: 1. pitavastatin monotherapy 2. monotherapy with a PCSK9 inhibitor (evolocumab 140 mg or alirocumab 150 mg once every 2 weeks subcutaneously) In the group of PCSK9 inhibitors:The lipid profile and safety of the therapy will be assessed in 1, 3 and 6 months after the start of the therapy. When triglyceride levels rise above 5.7 mmol/l in two consecutive analyzes, the addition of fenofibrate may be considered. Second phase (6 months): If the target level of LDL-C is not achieved during monotherapy with a PCSK9 inhibitor, the patient will be asked to continue treatment with combined lipid-lowering therapy (pitavastatin + PCSK9 inhibitor). Pitavastatin will initially be prescribed at a dose of 2 mg, after 1 month. in the absence of side effects against the background of ongoing therapy, the dose will be increased to 4 mg. There will be visits on the 7th, 9th and 12th months.

Arms:

PCSK9 Inhibitors

Size

Primary endpoint

absolute change in LDL-C from baseline by months 1 and 3 of study therapy

months 1 and 3 of study therapy

percent change in LDL-C from baseline at months 1 and 3 of study therapy

months 1 and 3 of study therapy

the proportion of patients who have reached the target level of LDL-C by month 1 of study therapy

month 1 of study therapy

the proportion of patients who have reached the target level of LDL-C by month 3 of study therapy

month 3 of study therapy

Eligibility criteria

Inclusion Criteria: * signed informed consent to participate in the study; * a history of liver transplantation for any reason; * immunosuppressive therapy; * the presence of hyperlipidemia, requiring the prescription of lipid-lowering therapy according to the clinical guidelines of the European Society for the Study of Atherosclerosis (EAS) 2019 * failure to achieve the target level of LDL-C against the background of current lipid-lowering therapy; * if the patient within 1 month before randomization took lipid-lowering therapy, then the absence of side effects against the background of previous lipid-lowering therapy. Exclusion Criteria: * treatment with PCSK9 in previous 6 months; * current treatment in the form of lipoprotein apheresis; * heart failure IV NYHA; * active infectious disease, severe hematological, metabolic, gastrointestinal or endocrine dysfunctions (for example, uncontrolled thyroid dysfunction) at the time of the screening or randomization visits; * the presence of an oncological disease, with the exception of hepatocellular carcinoma, which served as the reason for liver transplantation; * CFR\<15ml/min/1,73m2; * pregnancy and breastfeeding.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'phase 1: randomized, prospective, single-center, parallel-group study\n\nphase 2: observational study', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 80, 'type': 'ESTIMATED'}}

Updated at

2024-02-26

1 organization

2 products

5 indications

Organization

National Medical Research Center for Therapy and Preventive Medicine

Product

Pitavastatin

Indication

Dyslipidemia

Indication