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

Dyslipidemias Clinical Trial

— PINTL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05537948
• Other study ID #: 2.0_17.03.22
• Status: Recruiting
• Phase: Phase 4
• Start date: October 1, 2021
• Est. completion date: January 31, 2025

Study information

• Verified date: February 2024
• Source: National Medical Research Center for Therapy and Preventive Medicine
• Contact: Alexandra Ershova, PhD
• Phone: +79165598536
• Email: alersh[@]mail.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 31, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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.
• 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.

Locations

Country	Name	City	State
Russian Federation	National Medical Research Centre for Therapy and Preventive Medicine of the Ministry of Health of Russia	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
National Medical Research Center for Therapy and Preventive Medicine

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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