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

Primary Purpose

Dyslipidemias, Hyperlipidemias, Liver Transplant Disorder

Status

Recruiting

Phase

Phase 4

Locations

Russian Federation

Study Type

Interventional

Intervention

Pitavastatin

PCSK9 inhibitor

About this trial

This is an interventional treatment trial for Dyslipidemias focused on measuring Dyslipidemias, Hyperlipidemias, Liver Transplant Disorder, Immunosuppression, Immunosuppressive therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, pitavastatin, statins, PCSK9, PCSK9 Inhibitors, evolocumab, alirocumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

pitavastatin

PCSK9 Inhibitors

Arm Description

Pitavastatin 2 mg/d - 4 mg/d

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

Outcomes

Primary Outcome Measures

absolute change in LDL-C from baseline by 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

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

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

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

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

percent of patients with target level of LDL-C

Full Information

NCT ID

NCT05537948

First Posted

July 1, 2022

Last Updated

September 8, 2022

Sponsor

National Medical Research Center for Therapy and Preventive Medicine

1. Study Identification

Unique Protocol Identification Number

NCT05537948

Brief Title

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

Acronym

PINTL

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

October 1, 2021 (Actual)

Primary Completion Date

September 1, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Medical Research Center for Therapy and Preventive Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

InvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

pitavastatin

Arm Type

Active Comparator

Arm Description

Pitavastatin 2 mg/d - 4 mg/d

Arm Title

PCSK9 Inhibitors

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Pitavastatin

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

PCSK9 inhibitor

Intervention Description

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.

Primary Outcome Measure Information:

Title

absolute change in LDL-C from baseline by months 1 and 3 of study therapy

Description

absolute change in LDL-C from baseline

Time Frame

months 1 and 3 of study therapy

Title

percent change in LDL-C from baseline at months 1 and 3 of study therapy

Description

percent change in LDL-C from baseline

Time Frame

months 1 and 3 of study therapy

Title

the proportion of patients who have reached the target level of LDL-C by month 1 of study therapy

Description

the proportion of patients who have reached the target level of LDL-C

Time Frame

month 1 of study therapy

Title

the proportion of patients who have reached the target level of LDL-C by month 3 of study therapy

Description

the proportion of patients who have reached the target level of LDL-C

Time Frame

month 3 of study therapy

Secondary Outcome Measure Information:

Title

the timing of achieving the target level of LDL-C at months 1, 3, 6, 7, 9, 12 of study therapy

Description

the timing of achieving the target level of LDL-C

Time Frame

months 1, 3, 6, 7, 9, 12 of study therapy

Title

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

Description

percent of patients with target level of LDL-C

Time Frame

months 6 and 12 of study therapy

Other Pre-specified Outcome Measures:

Title

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

Description

the proportion of patients with increased level of creatine phosphokinase (more than 4 times of the upper limit normal (ULN))

Time Frame

months 1, 3, 6, 7, 9, 12 of study therapy

Title

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

Description

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

Time Frame

months 1, 3, 6, 7, 9, 12 of study therapy

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Alexandra Ershova, PhD

Phone

+79165598536

alersh@mail.ru

First Name & Middle Initial & Last Name or Official Title & Degree

Alexey Kucherov, MD

Phone

+7(985)774-44-05

kucherovalexey@yandex.ru

Facility Information:

Facility Name

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

City

Moscow

ZIP/Postal Code

101000

Country

Russian Federation

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alexandra Ershova, MD, PhD

Phone

+79165598536

alersh@mail.ru

First Name & Middle Initial & Last Name & Degree

Oksana Kopylova, MD

Phone

+79261786358

sivoksana@yandex.ru

First Name & Middle Initial & Last Name & Degree

Oxana Drapkina, MD, PhD

First Name & Middle Initial & Last Name & Degree

Alexandra Ershova, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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