Clinical trial NCT05537948: Efficacy and Safety of Pitavastatin and PCSK9 Inhibitors in Liver Transplant Patients
Official title: Efficacy and Safety of Pitavastatin and PCSK9 Inhibitors in Liver Transplant Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
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
Lead sponsor: National Medical Research Center for Therapy and Preventive Medicine
Sponsor class: OTHER_GOV
First posted: 2022-09-13
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: phase 1: randomized, prospective, single-center, parallel-group study

phase 2: observational study
Primary purpose: TREATMENT

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

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.

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.

Primary outcomes:
measure: absolute change in LDL-C from baseline by months 1 and 3 of study therapy
timeFrame: months 1 and 3 of study therapy
measure: percent change in LDL-C from baseline at months 1 and 3 of study therapy
timeFrame: months 1 and 3 of study therapy
measure: the proportion of patients who have reached the target level of LDL-C by month 1 of study therapy
timeFrame: month 1 of study therapy
measure: the proportion of patients who have reached the target level of LDL-C by month 3 of study therapy
timeFrame: month 3 of study therapy
Secondary outcomes:
measure: the timing of achieving the target level of LDL-C at months 1, 3, 6, 7, 9, 12 of study therapy
timeFrame: months 1, 3, 6, 7, 9, 12 of study therapy
measure: percent of patients with target level of LDL-C at months 6 and 12 of study therapy
timeFrame: months 6 and 12 of study therapy
Other outcomes:
measure: 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
timeFrame: months 1, 3, 6, 7, 9, 12 of study therapy
measure: 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
timeFrame: months 1, 3, 6, 7, 9, 12 of study therapy
Locations:
city: Moscow
country: Russian Federation
facility: National Medical Research Centre for Therapy and Preventive Medicine of the Ministry of Health of Russia
Study officials:
affiliation: National Medical Research Centre for Therapy and Preventive Medicine Ministry of Health of Russia
name: Alexandra Ershova, PhD
role: STUDY_CHAIR
References: