Effects of Clopidogrel on Blood Pressure

NCT01112137 | Completed Phase 4

• 1 other identifier: NLN5031
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 2

Brief Summary

Context: Soluble CD40 ligand (sCD40L) released from activated platelets induces inflammatory transformation of the vascular endothelium and is an independent predictor of cardiovascular events. Arterial hypertension is associated with platelet activation, increased sCD40L levels and endothelial dysfunction suggesting that inhibition of platelet-derived sCD40L release may improve endothelial function and lower blood pressure (BP). Objective: To determine the effects of clopidogrel on sCD40L, endothelial function and BP. Design: Randomized, controlled, investigator-blinded, parallel-group, 2-phase trial in patients with coronary artery disease and essential arterial hypertension and those without hypertension. Intervention: Participants receive a single 600-mg clopidogrel loading dose (phase I) followed by a daily 75-mg clopidogrel maintenance dose over 28 days (phase II). Outcome Measures: Primary outcome measure is the change in BP from baseline. Secondary outcome measures are changes in biomarkers of platelet and endothelial function and their correlation with BP.

Conditions

Blood Pressure; Endothelial Function; Platelet Function

Outcome Measures

Primary Outcomes (1)

• blood pressure

Secondary Outcomes (1)

• markers of platelet and endothelial function

Study Arms (4)

Hypertensive individuals: clopidogrel (600 mg, bolus)

EXPERIMENTAL

Drug: Clopidogrel

Hypertensive individuals: clopidogrel (75 mg daily)

EXPERIMENTAL

Drug: Clopidogrel

Normotensive individuals: clopidogrel (600 mg, bolus)

ACTIVE COMPARATOR

Drug: Clopidogrel

Normotensive individuals: clopidogrel (75 mg, daily)

ACTIVE COMPARATOR

Drug: Clopidogrel

Interventions

Clopidogrel DRUG

Hypertensive individuals: clopidogrel (600 mg, bolus)

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with coronary artery disease (CAD) and a clinical presentation of stable angina pectoris or acute coronary syndrome who had undergone percutaneous coronary intervention (PCI) with stent implantation
• year history of essential arterial hypertension with a systolic BP between 140 and 170 mmHg or no hypertension (systolic BP \<140mg Hg and diastolic BP \<90 mmHg)
• treatment with clopidogrel (75 mg per day) for 6 to 12 months after PCI
• continuous use of aspirin (100 mg per day)
• no change in drug therapy within 3 months prestudy

You may not qualify if:

• stent thrombosis or another ischemic cardiovascular event following PCI
• use of other antiplatelet drugs or anticoagulants within 3 months prestudy
• surgery within 3 months prestudy
• arrhythmia
• valvular heart disease
• hematologic disorder
• severe renal disorder
• severe hepatic disorder
• chronic inflammatory disorder
• autoimmune disorder
• acute or chronic infection
• active malignancy
• a body-mass index below 18.5 or above 40 kg/m2
• nonadherence to therapy
• nonattendance to control visits

Sponsors & Collaborators

• University of Cologne: lead

Study Sites (2)

University of Cologne

Cologne, D-50931, Germany

Location

St Antonius Hospital Nieuwegein

Nieuwegein, 3435 CM, Netherlands

Location

Related Publications (4)

• Heeschen C, Dimmeler S, Hamm CW, van den Brand MJ, Boersma E, Zeiher AM, Simoons ML; CAPTURE Study Investigators. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med. 2003 Mar 20;348(12):1104-11. doi: 10.1056/NEJMoa022600.

  PMID: 12646667 BACKGROUND

• Heitzer T, Rudolph V, Schwedhelm E, Karstens M, Sydow K, Ortak M, Tschentscher P, Meinertz T, Boger R, Baldus S. Clopidogrel improves systemic endothelial nitric oxide bioavailability in patients with coronary artery disease: evidence for antioxidant and antiinflammatory effects. Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1648-52. doi: 10.1161/01.ATV.0000225288.74170.dc. Epub 2006 May 4.

  PMID: 16675725 BACKGROUND

• Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G, Kroczek RA. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature. 1998 Feb 5;391(6667):591-4. doi: 10.1038/35393.

  PMID: 9468137 BACKGROUND

• Chen C, Chai H, Wang X, Jiang J, Jamaluddin MS, Liao D, Zhang Y, Wang H, Bharadwaj U, Zhang S, Li M, Lin P, Yao Q. Soluble CD40 ligand induces endothelial dysfunction in human and porcine coronary artery endothelial cells. Blood. 2008 Oct 15;112(8):3205-16. doi: 10.1182/blood-2008-03-143479. Epub 2008 Jul 24.

  PMID: 18658029 BACKGROUND

MeSH Terms

Interventions

Clopidogrel

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 26, 2010
• First Posted: April 28, 2010
• Study Start: January 1, 2005
• Primary Completion: December 1, 2009
• Study Completion: April 1, 2010
• Last Updated: April 28, 2010

Record last verified: 2010-04

Locations

DE (1); NL (1)