Investigation of Nickel Sensitization After Percutaneous Implantation of Patent Foramen Ovale Occluder

Study Overview
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Brief Summary
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Percutaneous PFO closure has been established as a first-line therapy for preventing recurrent strokes in selected patients. The devices used for the specific purpose contain and release nickel, which is considered as the most allergen metal in nature. Skin patch tests are considered as gold-standard for documenting nickel allergy. While the allergic contact dermatitis induced by nickel is well described, literature is inadequate on explaining the effect of nickel release on the clinical manifestations of patients implanted with such devices. Our prospective, randomized, blinded trial will try to investigate the above by performing nickel skin patch tests to all patients, 14 days before and 90 days after the implantation. During follow-up, clinical manifestations and transthoracic echocardiographic findings will be evaluated and associated with patch skin tests.

Detailed Description
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Percutaneous PFO closure has been established as a first-line therapy for preventing recurrent strokes, after embolic stroke of unknown source (ESUS) and a patent foramen ovale. The PFO closure is achieved by the implantation of suitable devices, which occlude the shunt between the two atria and prevent the creation and detachment of thrombi. Until today, there are two devices approved by FDA for the specific purpose; Amplatzer PFO Occluder and Gore Cardioform Septal Occluder. Despite the architectonic differences between these devices, the main material of both is nitinol, an alloy of nickel and titanium. While titanium is an extremely rare allergen, nickel is considered as one of the most common allergens and the most frequent metal allergen in nature, with a prevalence about 20%. The main clinical expression of nickel hypersensitivity is allergic contact dermatitis, but cases with systemic allergic reaction have been described as well. It has been observed that nickel is released by the implanted devices and circulates through bloodstream, having the potential to cause systemic clinical picture. Device syndrome includes signs and symptoms (i.e. palpitations, dyspnea, chest pain, rash, etc.), which are appeared after the device placement and are associated with hypersensitivity reaction. The existing literature is considered as inadequate for explaining the effect of nickel release in the patients implanted with an occluder. Our trial will try to investigate the impact of device placement to nickel skin patch test results and the correlation with the clinical manifestations of patients. Considering that, skin patch tests for nickel and other allergens will be performed in all included patients, 14 days prior and 90 days after the procedure. The patients will be randomized to receive either Amplatzer or Gore device, with parallel assignment and randomization 1:1. During follow-up, clinical manifestations and transthoracic echocardiographic findings will be evaluated and associated with patch skin tests. The time frame of 90 days has been selected, due to the duration of device's endothelization and nickel release.

Official Title
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Investigation of Nickel Sensitization After Percutaneous Implantation of Patent Foramen Ovale Occluder; a RandomizEd Trial.

Conditions
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Foramen Ovale, Patent, Nickel Sensitivity, Dermatitis Contact Irritant, Metal Allergy

Intervention / Treatment
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* Device: Percutaneous Patent Foramen Ovale Closure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: at least 14 years old Well-documented indication for percutaneous PFO closure Exclusion Criteria: Severe periprocedural complications (death, device embolization, major bleeding, etc) Patient's refusal to participation

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amplatzer PFO Occluder<br>Patients randomized in this arm will be implanted with Amplatzer PFO Occluder. | Device: Percutaneous Patent Foramen Ovale Closure<br>* Patients with well-documented embolic stroke of unknown source (ESUS) and a patent foramen ovale (PFO) are indicated for percutaneous closure of PFO. The intervention is performed through the right femoral vein. The interventional cardiologist introduces the sheath and advances the device via inferior vena cava to right atrium. Then, the catheter is passed through the PFO, the device is deployed and the occlusion is achieved. The procedure is performed under fluoroscopy guidance with or without transesophageal echocardiography guidance.<br>* Other names: Transcatheter PFO occlusion;|
| Active Comparator: Gore Cardioform Septal<br>Patients randomized in this arm will be implanted with Gore Cardioform Septal Occluder. | Device: Percutaneous Patent Foramen Ovale Closure<br>* Patients with well-documented embolic stroke of unknown source (ESUS) and a patent foramen ovale (PFO) are indicated for percutaneous closure of PFO. The intervention is performed through the right femoral vein. The interventional cardiologist introduces the sheath and advances the device via inferior vena cava to right atrium. Then, the catheter is passed through the PFO, the device is deployed and the occlusion is achieved. The procedure is performed under fluoroscopy guidance with or without transesophageal echocardiography guidance.<br>* Other names: Transcatheter PFO occlusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome including patient-reported chest pain, palpitations, headaches, and rash. | Clinical signs and symptoms during the first 90 days after the procedure will be evaluated through a questionnaire. | The first 90 days after the procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The nickel patch tests' results change after Amplatzer Device implantation | Investigating the number of patients received Amplatzer device, who developed nickel sensitization. | The first 90 days after the procedure | 
| The nickel patch tests' results change after Gore Device implantation | Investigating the number of patients received Gore device, who developed nickel sensitization. | The first 90 days after the procedure | 
| Residual interatrial leakage | Evaluation of residual interatrial leakage, by performing transthoracic echocardiography | 90 days after the procedure | 
| Rest allergens skin patch test results' change | The possible change (either as continuous or dichotomous outcome) of rest allergen skin patch test, after the device implantation | 90 days after the procedure | 
| Nickel patch test results' change | The possible change (either as continuous or dichotomous outcome) of nickel skin patch test, after the device implantation | 90 days after the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patent foramen ovale, percutaneous pfo closure, Nickel Hypersensitivity, Nickel Sensitisation, device syndrome, skin patch tests