Fixed Combination for Lipid and Blood Pressure Control

Overview

The aim of this study is to compare the effect of fixed and free combination of atorvastatin/perindopril/amlodipine on blood pressure and lipid levels.

Full Title of Study: “Fixed Combination for Lipid and Blood Pressure Control. Randomized Cross-over Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 31, 2019

Interventions

  • Drug: Atorvastatin, Amlodipine, Perindopril
    • To compare free and fixed combination of atorvastatin, perindopril, amlodipine

Arms, Groups and Cohorts

  • Active Comparator: Free combination
    • Free combination of atorvastatin, perindopril and amlodipine will be given for 8 weeks. After 8 weeks free combination will be changed to fixed combination. The dose of each drug will be selected according to clinical judgement of each investigator, but can not be changed during the coarse of the study.
  • Active Comparator: Fixed combination
    • Fixed combination of atorvastatin, perindopril and amlodipine will be given for 8 weeks. After 8 weeks fixed combination will be changed to free combination. The dose of each drug will be selected according to clinical judgement of each investigator, but can not be changed during the coarse of the study.

Clinical Trial Outcome Measures

Primary Measures

  • Blood pressure control
    • Time Frame: 16 weeks – 8 weeks fixed and 8 weeks free combination atorvastatin, perindopril, amlodipine
    • To compare the effect of fixed and free combination of atorvastatin/perindopril/amlodipine on 24h and in clinic blood pressure over the 16 weeks follow up.
  • Lipids control
    • Time Frame: 16 weeks – 8 weeks fixed and 8 weeks free combination atorvastatin, perindopril, amlodipine
    • To compare the effect of fixed and free combination of atorvastatin/perindopril/amlodipine on LDL cholesterol levels over the 16 weeks follow up.

Secondary Measures

  • Adherence
    • Time Frame: 16 weeks – 8 weeks fixed and 8 weeks free combination atorvastatin, perindopril, amlodipine
    • 1. To compare the effect of fixed and free combination of atorvastatin/perindopril/amlodipine on adherence evaluated by the Morisky medication adherence scale 8 and tablet counting over the 16 weeks follow up.
  • Blood pressure variability
    • Time Frame: 16 weeks – 8 weeks fixed and 8 weeks free combination atorvastatin, perindopril, amlodipine
    • To compare the effect of fixed and free combination of atorvastatin/perindopril/amlodipine on 24h blood pressure variability over the 16 weeks follow up.
  • Arterial properties
    • Time Frame: 16 weeks – 8 weeks fixed and 8 weeks free combination atorvastatin, perindopril, amlodipine
    • o compare the effect of fixed and free combination of atorvastatin/perindopril/amlodipine on arterial properties and central hemodynamic parameters measured during the 24 monitoring by the Mobilograph device over the 16 weeks follow up.

Participating in This Clinical Trial

Inclusion Criteria

Patients with uncontrolled arterial hypertension (the average 24h blood pressure in the range 130/80 – 180/110 mmHg and / or daytime average blood pressure in the range 135/85-180/110 mmHg) and one of the following: 1. a very high cardiovascular risk and LDL-cholesterol> 1.8 mmol / l 2. a high cardiovascular risk and LDL-cholesterol> 2.5 mmol / l 3. Patient with a high or very high cardiovascular risk treated by lipidlowering therapy with statin Exclusion Criteria:

1. hypersensitivity to perindopril or to other ACE inhibitors, amlodipine, atorvastatin, dihydropyridines or to or statins 2. angioneurotic edema in medical history (hereditary / idiopathic or associated with prior treatment with ACE inhibitors) 3. severe hypotension, shock, including cardiogenic shock 4. hemodynamically unstable heart failure 5. Active liver disease or unexplained persistent elevations of serum transaminases more than three times normal 6. Women of childbearing age without reliable contraception 7. pregnancy 8. breastfeeding 9. Patients with contraindications listed in the currently valid SP

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Charles University, Czech Republic
  • Collaborator
    • University Hospital Olomouc
  • Provider of Information About this Clinical Study
    • Principal Investigator: Peter Wohlfahrt, Peter Wohlfahrt, MD, PhD – Charles University, Czech Republic

References

Lawes CM, Vander Hoorn S, Rodgers A; International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet. 2008 May 3;371(9623):1513-8. doi: 10.1016/S0140-6736(08)60655-8.

Stamler J, Wentworth D, Neaton JD. Prevalence and prognostic significance of hypercholesterolemia in men with hypertension. Prospective data on the primary screenees of the Multiple Risk Factor Intervention Trial. Am J Med. 1986 Feb 14;80(2A):33-9. doi: 10.1016/0002-9343(86)90158-0.

Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension. 2010 Feb;55(2):399-407. doi: 10.1161/HYPERTENSIONAHA.109.139816. Epub 2009 Dec 21.

Grimm R, Malik M, Yunis C, Sutradhar S, Kursun A; TOGETHER Investigators. Simultaneous treatment to attain blood pressure and lipid goals and reduced CV risk burden using amlodipine/atorvastatin single-pill therapy in treated hypertensive participants in a randomized controlled trial. Vasc Health Risk Manag. 2010 May 6;6:261-71. doi: 10.2147/vhrm.s7710.

Malekzadeh F, Marshall T, Pourshams A, Gharravi M, Aslani A, Nateghi A, Rastegarpanah M, Khoshnia M, Semnani S, Salahi R, Thomas GN, Larijani B, Cheng KK, Malekzadeh R. A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy ('polypill') on cardiovascular risk factors. Int J Clin Pract. 2010 Aug;64(9):1220-7. doi: 10.1111/j.1742-1241.2010.02412.x.

Neutel JM, Bestermann WH, Dyess EM, Graff A, Kursun A, Sutradhar S, Yunis C. The use of a single-pill calcium channel blocker/statin combination in the management of hypertension and dyslipidemia: a randomized, placebo-controlled, multicenter study. J Clin Hypertens (Greenwich). 2009 Jan;11(1):22-30. doi: 10.1111/j.1751-7176.2008.00058.x.

PILL Collaborative Group; Rodgers A, Patel A, Berwanger O, Bots M, Grimm R, Grobbee DE, Jackson R, Neal B, Neaton J, Poulter N, Rafter N, Raju PK, Reddy S, Thom S, Vander Hoorn S, Webster R. An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk. PLoS One. 2011;6(5):e19857. doi: 10.1371/journal.pone.0019857. Epub 2011 May 25. Erratum In: PLoS One. 2019 Nov 25;14(11):e0225924.

Wald DS, Morris JK, Wald NJ. Randomized Polypill crossover trial in people aged 50 and over. PLoS One. 2012;7(7):e41297. doi: 10.1371/journal.pone.0041297. Epub 2012 Jul 18.

Indian Polycap Study (TIPS); Yusuf S, Pais P, Afzal R, Xavier D, Teo K, Eikelboom J, Sigamani A, Mohan V, Gupta R, Thomas N. Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial. Lancet. 2009 Apr 18;373(9672):1341-51. doi: 10.1016/S0140-6736(09)60611-5. Epub 2009 Mar 30.

Thom S, Poulter N, Field J, Patel A, Prabhakaran D, Stanton A, Grobbee DE, Bots ML, Reddy KS, Cidambi R, Bompoint S, Billot L, Rodgers A; UMPIRE Collaborative Group. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. JAMA. 2013 Sep 4;310(9):918-29. doi: 10.1001/jama.2013.277064. Erratum In: JAMA. 2013 Oct 9;310(14):1507. Naik, Nitish [added]; Reddy, Srinivas [added]; Balaji, Sham [corrected to Achuthan, Shyambalaji]; Damodra Rao, Modem [corrected to Damodra Rao, Kodem].

Soliman EZ, Mendis S, Dissanayake WP, Somasundaram NP, Gunaratne PS, Jayasingne IK, Furberg CD. A Polypill for primary prevention of cardiovascular disease: a feasibility study of the World Health Organization. Trials. 2011 Jan 5;12:3. doi: 10.1186/1745-6215-12-3.

Cho EJ, Kim JH, Sutradhar S, Yunis C, Westergaard M; CRUCIAL trial investigators. Reduction in cardiovascular risk using a proactive multifactorial intervention is consistent among patients residing in Pacific Asian and non-Pacific Asian regions: a CRUCIAL trial subanalysis. Vasc Health Risk Manag. 2014 Mar 26;10:145-56. doi: 10.2147/VHRM.S54586. eCollection 2014.

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