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

NCT ID: NCT05537948

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2025-01-31

Brief Summary

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

Detailed Description

1. Evaluate the efficacy and safety of lipid-lowering therapy in real clinical practice.

2. To evaluate the efficacy and safety of pitavastatin in patients undergoing liver transplantation and receiving immunosuppressive therapy.

3. Evaluate the efficacy and safety of PCSK9 inhibitors in patients undergoing liver transplantation and receiving immunosuppressive therapy.

4. To compare the efficacy and safety of pitavastatin and a PCSK9 inhibitor in patients undergoing liver transplantation and receiving immunosuppressive therapy.

Conditions

Dyslipidemias; Hyperlipidemias; Liver Transplant Disorder; Immunosuppression; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Statins

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

pitavastatin

Pitavastatin 2 mg/d - 4 mg/d

Group Type: ACTIVE_COMPARATOR

Pitavastatin

Intervention Type: DRUG

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.

PCSK9 Inhibitors

Evolocumab 140 mg once per 2 weeks or Alirokumab 150 mg once per 2 weeks

Group Type: ACTIVE_COMPARATOR

PCSK9 inhibitor

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Medical Research Center for Therapy and Preventive Medicine

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandra Ershova, PhD

Role: STUDY_CHAIR

National Medical Research Centre for Therapy and Preventive Medicine Ministry of Health of Russia

Locations

National Medical Research Centre for Therapy and Preventive Medicine of the Ministry of Health of Russia

Moscow, , Russia

Countries

Russia

Other Identifiers

2.0_17.03.22

Identifier Type: -

Identifier Source: org_study_id