The PostprAndial eNdothelial Function After Combination of Ezetimibe and simvAstatin Study (PANACEA)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
dr.Frank L.J. Visseren, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00817843
First received: January 6, 2009
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to investigate whether low-dose simvastatin in combination with ezetimibe in comparison to high-dose simvastatin alone, has a beneficial effect on the function of the endothelium after an oral fat load in patients with metabolic syndrome.


Condition Intervention Phase
Metabolic Syndrome
Drug: Simvastatin
Drug: Simvastatin/Ezetimibe
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multicenter,Double Blind,Randomized, 2-period, Crossover Study to Compare Ezetimibe/Simvastatin (10mg/10 mg) Combination Tablet Versus Simvastatin 80mg Tablet on Postprandial Arterial Endothelial Function in Patients With Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • Treatment Difference in (Postprandial-Fasting) FMD [ Time Frame: After 6 weeks of treatment ] [ Designated as safety issue: No ]
    A comparison of the postprandial minus fasting change in FMD under treatment with simvastatin 80 mg versus simvastatin 10/10 mg


Secondary Outcome Measures:
  • Postprandial Endopat Measurement [ Time Frame: after 6 weeks of treatment (crossover) ] [ Designated as safety issue: No ]
  • Preprandial Endothelial Function Measured by FMD [ Time Frame: after 6 weeks of treatment (crossover) ] [ Designated as safety issue: No ]
  • Preprandial Endopat Measurement [ Time Frame: after 6 weeks of treatment (crossover) ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: April 2009
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: First Simva 80mg then Simvai/Eze10/10mg
First 6 weeks of Simvastatin 80mg, then 6 weeks of Simvastatin/Ezetimibe 10/10mg after 6 weeks of placebo washout
Drug: Simvastatin
6 weeks of treatment with simvastatin 80 mg
Other Name: Simvastatin (Zocor)
Drug: Simvastatin/Ezetimibe
6 weeks of treatment with simvastatin 10 mg / ezetimibe 10 mg combination
Other Name: Simvastatin/Ezetimibe (Zetia)
Experimental: First Simva/Eze 10/10mg then Simva 80mg
First 6 weeks of Simvastatin/Ezetimibe 10/10mg, then 6 weeks of Simvastatin 80mg after 6 weeks of placebo washout
Drug: Simvastatin
6 weeks of treatment with simvastatin 80 mg
Other Name: Simvastatin (Zocor)
Drug: Simvastatin/Ezetimibe
6 weeks of treatment with simvastatin 10 mg / ezetimibe 10 mg combination
Other Name: Simvastatin/Ezetimibe (Zetia)

Detailed Description:

Metabolic syndrome is defined as a group of cardiovascular risk factors and is mainly driven by the epidemic of obesity. High blood lipid levels after a meal may be an important risk factor for cardiovascular disease. In this study we will investigate whether simvastatin in combination with ezetimibe vs. simvastatin alone, has a beneficial effect on the lipid levels after a meal, but more importantly, whether we can measure a difference in function of the endothelium. In a small pilot study we already found that the combination had a beneficial effect in comparison with simvastatin alone. Now we want to solidify these findings in a larger study.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  1. Patient has a diagnosis of metabolic syndrome according to the modified 2005 AHA/NHLBI Scientific Statement with at least:

    - Abdominal obesity defined as:

    *Males: waist circumference >102cm

    • Females: waist circumference >88cm and two of the following 4 other criteria:

      - Triglycerides>150 mg/dL

      - HDL Cholesterol

    • Males: HDL-C<40 mg/dL
    • Females:HDL-C<50 mg/dL - Blood pressure
    • Systolic Blood Pressure ≥130 mmHg or
    • Diastolic Blood Pressure ≥85 mmHg

      • Fasting glucose ≥ 100 mg/dL
  2. Patient understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
  3. Patient is a male or female of 18-79 years of age on the day of signing informed consent.
  4. Patient is a non-smoker.
  5. Patient is willing to maintain a stable diet for the duration of the study.
  6. Patient is a postmenopausal female who is not receiving hormone therapy (including cyclic and non-cyclical hormone replacement therapy or any estrogen antagonist/agonist). Postmenopausal status is defined as (1) no menses for ≥1 year but <3 years and confirmed by FSH levels elevated into the postmenopausal range (as defined by the designated laboratory) or (2) no menses for at least 3 years.
  7. Patient is naïve to lipid-lowering therapy. Naïve is defined as not being treated with a statin, a fibrate or ezetimibe for 3 months before Visit 1 (Week -2)
  8. Patient has a baseline fasting LDL-C level of ≥ 100 mg/dL and < 220 mg/dL, and TG level < 400 mg/dL.

EXCLUSION CRITERIA:

  1. Patient has a BMI > 35.
  2. Patient has hypersensitivity or intolerance to ezetimibe or simvastatin or any component of these medications, or to latex.
  3. Patient routinely consumes more than 14 alcoholic drinks per week.
  4. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.
  5. Patient has a smoking history > 10 pack-years (1 pack-year = at least 20 cigarettes per day for a year) OR patient who has smoked within 3 months prior to Visit 1 (Week -2).
  6. Patient has exclusionary laboratory values at Visit 1 (Week -2) as listed in the table below:

    liver transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) > 1.5 X ULN with no active liver disease Serum glucose > 7.0 mmol/L Creatine kinase(CK)> 2 X ULN Albumin:creatinine ratio > 34 TSH <0.3 mcIU/mL or > 5.0 mcIU/mL

  7. Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
  8. It is not possible to obtain a FMD measurement of sufficient quality at screening (Visit 1)
  9. Patient has congestive heart failure, atherosclerotic vascular disease or acute or chronic coronary heart disease.

13. Patient has had a partial ileal bypass, gastric bypass, gastric banding, celiac disease or other significant intestinal malabsorption.

15. Patient has untreated and uncontrolled hypertension with systolic blood pressure >160 mm Hg or diastolic >100 mm Hg at Visit 1 (Week -2). (Patients with untreated hypertension and with office BP at Visit 1 and Visit 2 averaging 160/100 or less can be enrolled). Patients using blood pressure-lowering medication are excluded.

16. Patient has estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 based on the 4-variable MDRD

17. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins at Visit 1 (Week -2).

18. Patient has diabetes mellitus defined as a history of diabetes or fasting serum glucose > 126 mg/dL.

For the full exclusion criteria, please check the protocol

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00817843

Locations
Netherlands
Academic Medical Center
Amsterdam, Netherlands, 1005 AZ
Vascular Research Center Hoorn
Hoorn, Netherlands, 1624 NP
Department of Vascular Medicine UMC Utrecht
Utrecht, Netherlands, 3584 CX
Tweesteden Ziekenhuis
Waalwijk, Netherlands, 5141 BM
Spain
Hospital Arnau de Vilanova
Lleida, Spain, E-25198
Sponsors and Collaborators
dr.Frank L.J. Visseren
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Frank LJ Visseren, MD PhD UMC Utrecht
  More Information

Publications:
Responsible Party: dr.Frank L.J. Visseren, Professor F.L.J. Visseren, MD PhD, head of department of Vascular Medicine, UMC Utrecht
ClinicalTrials.gov Identifier: NCT00817843     History of Changes
Other Study ID Numbers: Vasc-UMCU-10B, 2008-003908-61
Study First Received: January 6, 2009
Results First Received: June 18, 2012
Last Updated: January 4, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Spanish Agency of Medicines

Keywords provided by UMC Utrecht:
Postprandial hypertriglyceridemia
Metabolic syndrome
Endothelial function
Flow mediated dilatation
EndoPAT
Simvastatin
Ezetimibe

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Simvastatin
Ezetimibe
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014