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

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

Study Overview

• Status: Recruiting
• Conditions: Dyslipidemias; Hyperlipidemias; Liver Transplant Disorder; Immunosuppression; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Statins
• Intervention / Treatment: Drug: Pitavastatin; Drug: PCSK9 inhibitor

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Alexandra Ershova, PhD; Phone Number: +79165598536; Email: alersh@mail.ru
• Study Contact Backup: Name: Alexey Kucherov, MD; Phone Number: +7(985)774-44-05; Email: kucherovalexey@yandex.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 101000
    • Recruiting
    • National Medical Research Centre for Therapy and Preventive Medicine of the Ministry of Health of Russia
    • Contact: Alexandra Ershova, MD, PhD; Phone Number: +79165598536; Email: alersh@mail.ru
    • Contact: Oksana Kopylova, MD; Phone Number: +79261786358; Email: sivoksana@yandex.ru
    • Principal Investigator: Oxana Drapkina, MD, PhD
    • Sub-Investigator: Alexandra Ershova, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	the proportion of patients with increased level of creatine phosphokinase (more than 4 times of the upper limit normal (ULN))	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 at 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	months 1, 3, 6, 7, 9, 12 of study therapy

Collaborators and Investigators

• Sponsor: National Medical Research Center for Therapy and Preventive Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: July 1, 2022
• First Submitted That Met QC Criteria: September 8, 2022
• First Posted (Actual): September 13, 2022

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Immunosuppression; PCSK9; Immunosuppressive therapy; Liver Transplant Disorder; statins; Dyslipidemias; PCSK9 Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; pitavastatin; alirocumab; evolocumab
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Serine Proteinase Inhibitors; Pitavastatin; PCSK9 Inhibitors
• Other Study ID Numbers: 2.0_17.03.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No