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

Sponsor

National Medical Research Center for Therapy and Preventive Medicine (Other)

Overall Status

Recruiting

CT.gov ID

NCT05537948

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemias Hyperlipidemias Liver Transplant Disorder Immunosuppression Hydroxymethylglutaryl-CoA Reductase Inhibitors Statins	Drug: Pitavastatin Drug: PCSK9 inhibitor	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

phase 1: randomized, prospective, single-center, parallel-group study phase 2: observational studyphase 1: randomized, prospective, single-center, parallel-group study phase 2: observational study

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 1, 2021

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: pitavastatin Pitavastatin 2 mg/d - 4 mg/d	Drug: Pitavastatin 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.
Active Comparator: PCSK9 Inhibitors Evolocumab 140 mg once per 2 weeks or Alirokumab 150 mg once per 2 weeks	Drug: PCSK9 inhibitor 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.

Arm

Intervention/Treatment

Active Comparator: pitavastatin

Pitavastatin 2 mg/d - 4 mg/d

Drug: Pitavastatin

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.

Active Comparator: PCSK9 Inhibitors

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

Drug: PCSK9 inhibitor

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.

Outcome Measures

Primary Outcome Measures

absolute change in LDL-C from baseline by months 1 and 3 of study therapy [months 1 and 3 of study therapy]
absolute change in LDL-C from baseline
percent change in LDL-C from baseline at months 1 and 3 of study therapy [months 1 and 3 of study therapy]
percent change in LDL-C from baseline
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
the proportion of patients who have reached the target level of LDL-C by month 3 of study therapy [month 3 of study therapy]
the proportion of patients who have reached the target level of LDL-C

Secondary Outcome Measures

the timing of achieving the target level of LDL-C at months 1, 3, 6, 7, 9, 12 of study therapy [months 1, 3, 6, 7, 9, 12 of study therapy]
the timing of achieving the target level of LDL-C
percent of patients with target level of LDL-C at months 6 and 12 of study therapy [months 6 and 12 of study therapy]
percent of patients with target level of LDL-C

Other Outcome Measures

the proportion of patients with increased level of creatine phosphokinase (more than 4 times of the upper limit normal (ULN)) at months 1, 3, 6, 7, 9, 12 of study therapy [months 1, 3, 6, 7, 9, 12 of study therapy]
the proportion of patients with increased level of creatine phosphokinase (more than 4 times of the upper limit normal (ULN))
the proportion of patients with increase higer than the upper limit normal (ULN) of one of the parameters in blood: ALT, AST, GGT, alkaline phosphatase, total bilirubin at months 1, 3, 6, 7, 9, 12 of study therapy [months 1, 3, 6, 7, 9, 12 of study therapy]
the proportion of patients with increase higer than the upper limit normal (ULN) of one of the parameters in blood: ALT, AST, GGT, alkaline phosphatase, total bilirubin

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.