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

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

Detailed Description
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Evaluate the efficacy and safety of lipid-lowering therapy in real clinical practice. To evaluate the efficacy and safety of pitavastatin in patients undergoing liver transplantation and receiving immunosuppressive therapy. Evaluate the efficacy and safety of PCSK9 inhibitors in patients undergoing liver transplantation and receiving immunosuppressive therapy. To compare the efficacy and safety of pitavastatin and a PCSK9 inhibitor in patients undergoing liver transplantation and receiving immunosuppressive therapy.

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

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

Intervention / Treatment
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* Drug: Pitavastatin
* Drug: PCSK9 inhibitor


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: phase 1: randomized, prospective, single-center, parallel-group study phase 2: observational study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: pitavastatin<br>Pitavastatin 2 mg/d - 4 mg/d | Drug: Pitavastatin<br>* First phase (6 months): Patients will be randomized 1:1 into 2 groups: pitavastatin monotherapy 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.<br>|
| Active Comparator: PCSK9 Inhibitors<br>Evolocumab 140 mg once per 2 weeks or Alirokumab 150 mg once per 2 weeks | Drug: PCSK9 inhibitor<br>* First phase (6 months): Patients will be randomized 1:1 into 2 groups: pitavastatin monotherapy 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| absolute change in LDL-C from baseline by months 1 and 3 of study therapy | absolute change in LDL-C from baseline | months 1 and 3 of study therapy | 
| percent change in LDL-C from baseline at months 1 and 3 of study therapy | percent change in LDL-C from baseline | 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 | the proportion of patients who have reached the target level of LDL-C | month 1 of study therapy | 
| the proportion of patients who have reached the target level of LDL-C by month 3 of study therapy | the proportion of patients who have reached the target level of LDL-C | month 3 of study therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the timing of achieving the target level of LDL-C at months 1, 3, 6, 7, 9, 12 of study therapy | the timing of achieving the target level of LDL-C | months 1, 3, 6, 7, 9, 12 of study therapy | 
| percent of patients with target level of LDL-C at months 6 and 12 of study therapy | percent of patients with target level of LDL-C | months 6 and 12 of study therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dyslipidemias, Hyperlipidemias, Liver Transplant Disorder, Immunosuppression, Immunosuppressive therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, pitavastatin, statins, PCSK9, PCSK9 Inhibitors, evolocumab, alirocumab