Metal Allergy In-Stent Restenosis Study (RESTALL)

RESTenosis in Patients With Contact ALLergy to Metals Zabrze Study

In-stent restenosis remains one of the most challenging problems in patients after coronary artery angioplasty. Angiographically, it is discovered in 10% of the patients after drug-eluting stent (DES) implantation. There are multiple factors causing restenosis, which can be divided into two major groups: first vessel-dependent (based on the vessel's tortuosity, dimensions and lesion's calcification, all leading to suboptimal stent expansion), and second dependent on the inflammatory processes caused by the intervention. Study objectives is the analysis of the possible correlation between allergy to metals utilised during the stent manufacturing (nickel, cobalt, chromium, molybdenum, tungsten) and in-stent restenosis occurence. The angiographic results of stent implantation, and in-stent restenosis will be assessed independently by two skilled interventional cardiologists, and in case of their discrepant opinions, the decision will be made on the basis of the third cardiologist. The tests will be applicated during the hospitalisation, then read after 48 hours and 72 hours, and subsequently interpreted by the skilled dermatologist, during the hospital stay or afterwards.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Restenoses, Coronary; In-stent Restenosis; Contact Allergy; Metal Allergy
• Intervention / Treatment: Biological: In-stent restenosis

Detailed Description

Introduction:

In-stent restenosis remains one of the most challenging problems in patients after coronary artery angioplasty. Angiographically, it is discovered in 10% of the patients after drug-eluting stent (DES) implantation. There are multiple factors causing restenosis, which can be divided into two major groups: first vessel-dependent (based on the vessel's tortuosity, dimensions and lesion's calcification, all leading to suboptimal stent expansion), and second dependent on the inflammatory processes caused by the intervention. Although the proper stent expansion depends mostly on the cardiologist's manual dexterity, the inflammation development does totally not depend on the operator. The allergic reactions to metals are likely to be one of the underlying causes of inflammation. Among the most prevalent allergens, cobalt, chromium, nickel, and tungsten used as the stent materials are causing the most intensive contact allergic reaction. The allergic process induced by the aforementioned metals belongs to type IV contact allergy (T-cell mediated). Stent implantation results in life-long contact with metal, thus in allergic patients, it is likely to develop local reactions leading to in-stent restenosis. Up to date, there have been approximately one thousand in-stent restenosis cases documented in patients with confirmed contact allergy to stent metals.

Study objectives:

Analysis of the possible correlation between allergy to metals utilised during the stent manufacturing (nickel, cobalt, chromium, molybdenum, tungsten) and in-stent restenosis occurence.

Materials and methods:

The study will consist of two arms:

First arm: Patch tests for the metals used in stent production will be applicated in the patients with angiographically proven in-stent restenosis developed after technically correct implantation.

Second arm: In patients with (technically correctly) implanted stent, patch tests will be applicated to identify cases with contact allergy. The patients will then be monitored for a 6-12 months follow-up period in purpose of evaluating the dependance between in-stent restenosis and contact allergy.

The angiographic results of stent implantation, and in-stent restenosis will be assessed independently by two skilled interventional cardiologists, and in case of their discrepant opinions, the decision will be made on the basis of the third cardiologist.

The tests will be applicated during the hospitalisation, then read after 48 hours and 72 hours, and subsequently interpreted by the skilled dermatologist, during the hospital stay or afterwards.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• angiographically proven in-stent restenosis after technically correct implantation
• technically correctly implanted stent

Exclusion Criteria:

• autoimmune diseases (e.g., rheumatoid arthritis)
• immunodeficiency syndromes (e.g., HIV infection)
• chronic use of immunosuppressive drugs and/or corticosteroids
• skin lesions that may attenuate the reading of skin tests
• previous coronary artery bypass surgery (in subgroup 1) or planned coronary artery bypass surgery (in subgroup 2)
• any surgical procedure with metal implants (in the past or planned within 12 months of observation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metal allergy driven restenosis; Patients with angiographically proven in-stent restenosis developed after technically correct implantation. Patch tests for the metals used in stent production will be applicated. The tests will be applicated during the hospitalisation, then read after 48 hours and 72 hours, and subsequently interpreted by the skilled dermatologist, during the hospital stay or afterwards. Possible correlation between allergy to metals utilised during the stent manufacturing (nickel, cobalt, chromium, molybdenum, tungsten) and in-stent restenosis occurence.	Biological: In-stent restenosis; Patch tests for the metals applicated in each of the patients
Placebo Comparator: Looking for allergic restenosis; Patients with (technically correctly) implanted stent. Patch tests will be applicated to identify cases with contact allergy. The tests will be applicated during the hospitalisation, then read after 48 hours and 72 hours, and subsequently interpreted by the skilled dermatologist, during the hospital stay or afterwards.The patients will then be monitored for a 12 months follow-up period in purpose of evaluating the dependance between in-stent restenosis and contact allergy. Possible correlation between allergy to metals utilised during the stent manufacturing (nickel, cobalt, chromium, molybdenum, tungsten) and in-stent restenosis occurence.	Biological: In-stent restenosis; Patch tests for the metals applicated in each of the patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Cardiovascular Events (MACE)	In-stent restenosis, acute myocardial infarction (AMI), death, cardiovascular (CV) death	12 months

Collaborators and Investigators

• Sponsor: Silesian Centre for Heart Diseases

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2018
• Primary Completion (Anticipated): April 1, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: March 18, 2018
• First Submitted That Met QC Criteria: July 15, 2018
• First Posted (Actual): July 17, 2018

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: July 15, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: coronary artery disease; allergy to metals, restenosis, in-stent restenosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Dermatitis; Skin Diseases, Eczematous; Hypersensitivity, Delayed; Coronary Stenosis; Dermatitis, Contact; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Hypersensitivity; Dermatitis, Allergic Contact; Coronary Restenosis
• Other Study ID Numbers: RESTALL Zabrze Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No