Evaluation of Pitavastatin for efficacy and safety in Dyslipidemic patients:A comparative randomized controlled trial.

Phase 4

Recruiting

• Conditions: Dyslipidemic patients having hypertension, diabetes and / or coronary artery disease

• Registration Number: CTRI/2013/09/004003
• Lead Sponsor: Dr Chetan Yuvraj Patil

Brief Summary

Cardiovascular disease (CVD) is a major contributor to global morbidity, mortality and disability. Indeed, the WHO estimates that CVD accounted for 30% of global mortality during 2008. Numerous mutually reinforcing factors, including dyslipidemia, diabetes, hypertension contribute to CVD.Statins have contributed greatly to medical care since the late twentieth century through their role in the primary and secondary prevention of cardiovascular disease and reduction in total mortality.

Low-density lipoprotein cholesterol (LDL-C) level is thought to be most important predictor of the risk for cardiovascular disease. Aggressive lowering of LDL-C levels is associated with a greater risk reduction for cardiovascular disease.Also, HDL-C is considered to be the next important predictor of the risk for cardiovascular disease after LDL -C.

Statins are the competitive inhibitor of HMGCoA reductase, which is the rate-determining step in cholesterol biosynthesis. The use of these drugs has been associated with reductions in total cholesterol (TC) and LDL-C  and increase in HDL-C in a dose-dependent manner. Statins developed more recently exert more potent action on LDL-C reduction, also increasing the HDL-C levels.

Pitavastatin (NK-104, previously called itavastatin or nisvastatin) is a chemically synthesized statin, which was developed by Kowa Company Ltd. Tokyo, Japan in 2003. It is approved by the Food and Drug Administration (FDA) in the US in August 2009.It has been shown that pitavastatin is a powerful statin and has favourable pharmacokinetic properties which are likely to limit drug-drug interactions.Pitavastatin is currently indicated for patients with primary hyperlipidaemia and mixed dyslipidaemia to reduce total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), Apo lipoprotein B (Apo-B), triglycerides (TG),and to increase high-density lipoprotein cholesterol (HDL-C), in addition to diet. Pitavastatin is mainly excreted unchanged into faeces by the biliary route, with minimal renal elimination, with reported <4 % urinary excretion.

Atorvastatin is a potent and currently most widely used statin. Its effectiveness in lowering LDL cholesterol and total cholesterol (TC) has been demonstrated in a number of trials. However, it is metabolized by cytochrome p-450 and is therefore at an increased risk of drug–drug interactions. Also adverse events associated with atorvastatin and other current  statins (e.g. simvastatin and pravastatin) including myopathy, gastrointestinal disturbances, altered liver function tests, sleep disturbances, headache, paraesthesia and hypersensitivity reactions, risk of rhabdomyolysis (which, while rare, remains possibly the most serious adverse event associated with statins is 0.44 per 10,000 treatment-years for ) limits their safety.

Pitavastatin, the latest addition to the statin group has a higher afï¬nity for the HMG-CoA enzyme than other statins. Oral Absorption and Bioavailability of pitavastatin is about 80% and 60-80% respectively (compared to atorvastatin 30% and 12% respectively).  Pitavastatin is minimally metabolized in the liver by cytochrome p-450 as compared to atorvastatin and other currently used statins; also it undergoes limited glucuronidation and lactonization. Therefore it has low potential to interact with other drugs which may offer an advantage over other statins. Also ,Both pitavastatin and atorvastatin would be expected to be useful for lowering LDL-C in patients with dyslipidaemia ,but their effects on HDL-C have not been directly compared a much.

We therefore undertook this  prospective, controlled, randomized, double blind, comparative, parallel, 2-arm study to evaluate the efficacy and safety of Pitavastatin (4mg) Vs. Atorvastatin (20 mg) in patients with Dyslipidaemia associated with hypertension, diabetes and / coronary artery diseases.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01-11
• Last Update Posted: 2013-07-30

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• 1.Patients suffering from Dyslipidemia according to NCEP ATP III Guidelines (National Cholesterol Education Program, Adult Treatment Panel III) (LDL-C greater than or equal to 130 mg/dl, Total cholesterol- TC greater than or equal to 240 mg/dl) and associated with hypertension, diabetes and / coronary artery disease only.
• 2.Dyslipidemic patients, newly diagnosed or uncontrolled on monotherapy , 3.Non-pregnant, non-lactating female 4.Have given informed consent.

Exclusion Criteria

• 1.History of muscular or neuromuscular disease of any type 2.H/O chronic liver diseases 3.Impaired renal function 4.Concomitant medications such a cyclosporine A, gemfibrozil, clarithromycin, rafamycin, rafampicin, which might significantly cause drug-drug interaction.
• 5.History of drug allergy to study drugs related group 6.History of HIV infection 7.Diagnosed case any malignant condition, psychiatric illness 8.Patients addicted to alcohol 9.Exposure to any investigational new drug within 30 days of study entry or ingestion of any drug known to be toxic to a major organ system.
• 10.Serum total creatine kinase > 5x.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage Change From Baseline Low Density Lipoprotein Cholesterol(LDL-C)	Day 0, day 28 and day 56

Secondary Outcome Measures

Name	Time	Method
Percentage Change From Baseline High Density Lipoprotein Cholesterol(HDL-C)	Day 0, day 28 and day 56
Change From Baseline in Total Cholesterol (TC)
Percentage change in baseline LDLC/HDLC ratio	Day 0, day 28 and day 56
Percentage Change From Baseline triglyceride (TG)
Laboratory Parameters	Day 0, day 28 and day 56
Assessment of adverse events and serious adverse events	As and when they occur

Trial Locations

Locations (1)

Government Medical College; 🇮🇳 Aurangabad, MAHARASHTRA, India

Government Medical College

🇮🇳Aurangabad, MAHARASHTRA, India

Dr Chetan Yuvraj Patil

Principal investigator

9987442046

drchetanpatil.gmc@gmail.com