PROPIT: Study Evaluating Pitavastatin in Metabolic Syndrome
PROPIT: Study Evaluating Pitavastatin in Metabolic Syndrome
PROPIT was a prospective, randomized and multicenter open-label study conducted for 48 weeks at 10 different sites in Korea. The trial protocol was developed by the principal investigator group, and each researcher supervised the protocol. After the screening process, the selected patients were randomized into two groups: the pitavastatin (2 mg daily) + intensive LSM group or the intensive LSM only group. All the subjects were trained regarding LSM with the same protocol at the time of enrolment and were continuously managed and guided by health professionals of the Evercare Company. The LSM protocol included a weight-reduction diet program, projecting a 7–10% reduction in the initial body weight, and physical exercise for 30 min to 1 h per day, 4–5 times per week. The whole LSM program was Web-based, and the investigator/coordinator could give feedback via the website. The system included an online food diary, caloric information and exercise recommendations through the website home page or via text messages to the patients. The protocol compliance of the subjects was monitored by the coordinator with phone calls on a monthly basis, and the subjects were reminded of their performance in a weekly text message. Treatment with pitavastatin (2 mg daily) + LSM was used by the treatment group and only LSM was used by the control group. The subjects whose test results showed LDL ≥ 190 mg/dl or glycated haemoglobin (HbA1c) ≥ 8% at the 24-week (6-month) follow-up visit was withdrawn from the study because there was a drug-naïve arm in our study design. We followed up the subjects for 48 weeks (1 year) to compare the primary and secondary outcomes of the study. The study protocol is shown schematically in Fig. 1.
(Enlarge Image)
Figure 1.
Study design and the schematic flow of the PROPIT study.
The eligible patients were men and women aged 18–75 years with central obesity (waist circumference: men ≥ 90 cm, women ≥ 85 cm, according to the Korean Obesity Society and impaired fasting glucose (fasting glucose ≥ 100 mg/dl), which are essential components of MS, and one or more of the followings components: (i) triglyceride (TG) ≥ 150 mg/dl; (ii) high-density lipoprotein (HDL) for men ≤40 mg/dl, and for women ≤50 mg/dl; and (iii) systolic blood pressure (SBP) ≥ 130 mmHg or diastolic blood pressure (DBP) ≥ 85 mmHg. We enrolled all subjects with hypercholesterolaemia (LDL ≥ 100 mg/dl) to test the rationale of using statins for patients with MS. Subject should have no prior history of atherosclerosis or CVD. They were statin naïve, with no prior use of oral hypoglycaemic agents. We performed 75 g oral glucose tolerance test (OGTT) at the enrolment and excluded subjects who were defined as diabetes by 1997 ADA criteria. The exclusion criteria were the use of statins within the preceding 3 months; uncontrolled hypertension (DBP ≥ 95 mmHg); poorly controlled diabetes (HbA1c ≥ 8·0%); high cholesterolaemia (LDL ≥ 190 mg/dl or TG ≥ 400 mg/dl); a past medical history of coronary disease, atherosclerosis, malignancy or severe infective disease; renal dysfunction (creatinine ≥ 2·0 mg/dl) or hepatic dysfunction (aspartate aminotransferase or alanine aminotransferase ≥ upper normal limit [UNL] × 2·5); uncontrolled hypothyroidism (thyroid-stimulating hormone ≥ UNL × 1·5); creatine phosphokinase ≥ UNL × 2; pregnancy or possible pregnancy; and lactation. The study was conducted in accordance with the principles of the Declaration of Helsinki developed by the 52nd World Medical Association General Assembly. All patients were fully informed and their written consent was obtained. The approval of the Institutional Review of Board of Seoul National University Bundang Hospital and each participating hospital was obtained (IRB#:B-0801-053-010).
The primary end-point was the improvements in the components of MS and in the percentage of non-MS converters (participants who converted to non-MS status, MS score ≤2, after the trial) after the 1-year intervention. The secondary end-points included the changes from baseline in the Framingham risk score, lipid profiles (TG, HDL and LDL), apolipoprotein B/A1 (Apo B/A1) ratio, high-sensitivity C-reactive protein (hs-CRP), high molecular weight (HMW) adiponectin, abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) assessed with computed tomography (CT), homoeostatic model assessment (HOMA)-IR and glucose tolerance measured with the 75 g oral glucose tolerance test (OGTT).
We used the sas program (version 9·1·3) for all statistical analyses. The primary end-point and other parameters were analysed with a paired t-test when compared within groups (vs baseline) and a two-samples t-test when compared between groups. The χ-test was used to compare the categorical data and a two-samples t-test was used to compare the baseline parameters. The data are given as mean ± standard deviation or standard error of mean. Log transformation was performed to compare the value of TG. P < 0·05 was considered to be statistically significant.
Materials and Methods
Trial Design
PROPIT was a prospective, randomized and multicenter open-label study conducted for 48 weeks at 10 different sites in Korea. The trial protocol was developed by the principal investigator group, and each researcher supervised the protocol. After the screening process, the selected patients were randomized into two groups: the pitavastatin (2 mg daily) + intensive LSM group or the intensive LSM only group. All the subjects were trained regarding LSM with the same protocol at the time of enrolment and were continuously managed and guided by health professionals of the Evercare Company. The LSM protocol included a weight-reduction diet program, projecting a 7–10% reduction in the initial body weight, and physical exercise for 30 min to 1 h per day, 4–5 times per week. The whole LSM program was Web-based, and the investigator/coordinator could give feedback via the website. The system included an online food diary, caloric information and exercise recommendations through the website home page or via text messages to the patients. The protocol compliance of the subjects was monitored by the coordinator with phone calls on a monthly basis, and the subjects were reminded of their performance in a weekly text message. Treatment with pitavastatin (2 mg daily) + LSM was used by the treatment group and only LSM was used by the control group. The subjects whose test results showed LDL ≥ 190 mg/dl or glycated haemoglobin (HbA1c) ≥ 8% at the 24-week (6-month) follow-up visit was withdrawn from the study because there was a drug-naïve arm in our study design. We followed up the subjects for 48 weeks (1 year) to compare the primary and secondary outcomes of the study. The study protocol is shown schematically in Fig. 1.
(Enlarge Image)
Figure 1.
Study design and the schematic flow of the PROPIT study.
Study Subjects
The eligible patients were men and women aged 18–75 years with central obesity (waist circumference: men ≥ 90 cm, women ≥ 85 cm, according to the Korean Obesity Society and impaired fasting glucose (fasting glucose ≥ 100 mg/dl), which are essential components of MS, and one or more of the followings components: (i) triglyceride (TG) ≥ 150 mg/dl; (ii) high-density lipoprotein (HDL) for men ≤40 mg/dl, and for women ≤50 mg/dl; and (iii) systolic blood pressure (SBP) ≥ 130 mmHg or diastolic blood pressure (DBP) ≥ 85 mmHg. We enrolled all subjects with hypercholesterolaemia (LDL ≥ 100 mg/dl) to test the rationale of using statins for patients with MS. Subject should have no prior history of atherosclerosis or CVD. They were statin naïve, with no prior use of oral hypoglycaemic agents. We performed 75 g oral glucose tolerance test (OGTT) at the enrolment and excluded subjects who were defined as diabetes by 1997 ADA criteria. The exclusion criteria were the use of statins within the preceding 3 months; uncontrolled hypertension (DBP ≥ 95 mmHg); poorly controlled diabetes (HbA1c ≥ 8·0%); high cholesterolaemia (LDL ≥ 190 mg/dl or TG ≥ 400 mg/dl); a past medical history of coronary disease, atherosclerosis, malignancy or severe infective disease; renal dysfunction (creatinine ≥ 2·0 mg/dl) or hepatic dysfunction (aspartate aminotransferase or alanine aminotransferase ≥ upper normal limit [UNL] × 2·5); uncontrolled hypothyroidism (thyroid-stimulating hormone ≥ UNL × 1·5); creatine phosphokinase ≥ UNL × 2; pregnancy or possible pregnancy; and lactation. The study was conducted in accordance with the principles of the Declaration of Helsinki developed by the 52nd World Medical Association General Assembly. All patients were fully informed and their written consent was obtained. The approval of the Institutional Review of Board of Seoul National University Bundang Hospital and each participating hospital was obtained (IRB#:B-0801-053-010).
End-point Assessment
The primary end-point was the improvements in the components of MS and in the percentage of non-MS converters (participants who converted to non-MS status, MS score ≤2, after the trial) after the 1-year intervention. The secondary end-points included the changes from baseline in the Framingham risk score, lipid profiles (TG, HDL and LDL), apolipoprotein B/A1 (Apo B/A1) ratio, high-sensitivity C-reactive protein (hs-CRP), high molecular weight (HMW) adiponectin, abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) assessed with computed tomography (CT), homoeostatic model assessment (HOMA)-IR and glucose tolerance measured with the 75 g oral glucose tolerance test (OGTT).
Statistical Analysis
We used the sas program (version 9·1·3) for all statistical analyses. The primary end-point and other parameters were analysed with a paired t-test when compared within groups (vs baseline) and a two-samples t-test when compared between groups. The χ-test was used to compare the categorical data and a two-samples t-test was used to compare the baseline parameters. The data are given as mean ± standard deviation or standard error of mean. Log transformation was performed to compare the value of TG. P < 0·05 was considered to be statistically significant.
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