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

NCT05537948 | Active Not Recruiting Phase 4

• 1 other identifier: 2.0_17.03.22
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

Dyslipidemias; Hyperlipidemias; Liver Transplant Disorder; Immunosuppression; Immunosuppressive therapy; Hydroxymethylglutaryl-CoA Reductase Inhibitors; pitavastatin; statins; PCSK9; PCSK9 Inhibitors; evolocumab; alirocumab

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• 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

• percent of patients with target level of LDL-C at months 6 and 12 of study therapy

  months 6 and 12 of study therapy

Other Outcomes (2)

• 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 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

Study Arms (2)

pitavastatin

ACTIVE COMPARATOR

Pitavastatin 2 mg/d - 4 mg/d

Drug: Pitavastatin

PCSK9 Inhibitors

ACTIVE COMPARATOR

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

Drug: PCSK9 inhibitor

Interventions

Pitavastatin 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.

pitavastatin

PCSK9 inhibitor 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.

PCSK9 Inhibitors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

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

Moscow, 101000, Russia

Location

MeSH Terms

Conditions

Dyslipidemias; Hyperlipidemias

Interventions

pitavastatin

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Alexandra Ershova, PhD

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: July 1, 2022
• First Posted: September 13, 2022
• Study Start: October 1, 2021
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2025
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)