Erythrocyte-Mediated Drug Delivery for the Prevention of Stent Restenosis

Atherosclerosis Clinical Trial

— TROY  

Official title:

Erythrocyte-Mediated Drug Delivery for the Prevention of Restenosis After Coronary Artery Stent Implantation:TROY-Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00484965
• Other study ID #: 72/06
• Status: Not yet recruiting
• Phase: Phase 4
• First received: June 11, 2007
• Last updated: June 11, 2007
• Start date: July 2007
• Est. completion date: January 2009

Study information

• Verified date: June 2007
• Source: University of Rome Tor Vergata
• Contact: Francesco Versaci, MD, FACC
• Phone: +390620903536
• Email: francescoversaci[@]yahoo.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether erythrocyte mediated dexamethasone delivery reduces circulating inflammatory markers after coronary stent implantation and improves clinical and angiographic outcomes.

Description:

In stent restenosis is still an unsolved problem. We know that principally in stent restenosis depends on myointimal proliferation, a biological process in which inflammatory mechanisms play a central role. We have previously demonstrated that immunosuppressive therapy with prednisone administered for 45 days after the stenting procedure reduced the incidence of restenosis at six months and clinical events at 12 months in high risk patients, with persistent higher C reactive protein levels after stenting implantation. But this therapy needs a high dosage glucocorticoids, and this is a contraindication in some subset of patients i.e. diabetics.

Recently a new method for the encapsulation of drugs into human autologous erythrocytes using an apparatus and a disposable kit has been developed. It's well known that blood erythrocytes change their membrane properties when in contact with suspensions of different osmotic values. So we developed a method to modify erythrocytes membrane properties so that they became porous and be able to absorb and then release some specific molecules. Experimental studies demonstrated that non diffusible pro-drug 21-phosphate dexamethasone can be loaded in human blood erythrocytes and then slowly dephosphorylated to the corresponding diffusible molecule to be released in human plasma. Once in-vivo due to the presence of the hydrophilic phosphate group, Dex 21-P encapsulated into RBCs cannot diffuse through RBC membrane until it is slowly dephosphorylated to the corresponding active corticosteroid by erythrocytes resident enzymes. The novelty and the advantages of this procedure are that the red blood cells act as a slow and constant drug delivery system so that, during the 30 days after the administration, there is always a low level of corticosteroid in plasma. When these erythrocytes are reinfused in the donor, they release in a continuous way a low and constant level of drug. This procedure has yet been used in some chronic inflammatory disease (i.e. bowel disease) in more than 1600 patients, with significant clinical improvement. The main objective of the study is 1) to evaluate if autologous erythrocytes modified as bioreceptor may be used to release glucocorticoids in blood circulation and 2) to reduce acute inflammatory proteins after coronary stent implantation with clinical and angiographic outcomes improvement. For this purpose 100 patients undergoing coronary artery stent implantation will be prospectively randomized in two groups:

1. group A: bare metal stent implantation and treatment by 50 ml of autologous erythrocytes charged with dexamethasone 21-P

2. group B: bare metal stent implantation and treatment by 50 ml of autologous erythrocytes not charged with dexamethasone 21-P The results of two groups will be compared.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• coronary disease

• written informed consent

• coronary stenosis

• CRP baseline levels < 0,5 mg/dl

Exclusion Criteria:

• acute myocardial infarction

• coronary bypass grafting restenosis

• vessels diameter < 2,5 mm

• corticosteroids contraindications

• corticosteroids therapy 30 days before

• active infective disease

• connective disease

• pregnancy

• cancer

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute-Phase Reaction
• Atherosclerosis

Intervention

Procedure:
• Coronary stenting

Locations

Country	Name	City	State
Italy	Policlinico Tor Vergata	Rome

Sponsors (2)

Lead Sponsor	Collaborator
University of Rome Tor Vergata	University of Milan

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Versaci F, Gaspardone A, Tomai F, Ribichini F, Russo P, Proietti I, Ghini AS, Ferrero V, Chiariello L, Gioffrè PA, Romeo F, Crea F; Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation Study. Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS Study). J Am Coll Cardiol. 2002 Dec 4;40(11):1935-42. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine whether erythrocyte mediated dexamethasone delivery reduces circulating inflammatory markers after coronary stent implantation and improves reduction of acute phase reaction proteins		one year
Secondary	Reduction of myointimal proliferation and restenosis after stenting implantation		one year