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

Foramen Ovale, Patent Clinical Trial

— INSPIRE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04713683
• Other study ID #: NICKEL-PFO TRIAL
• Status: Recruiting
• Phase: N/A
• Start date: December 10, 2020
• Est. completion date: September 1, 2024

Study information

• Verified date: September 2023
• Source: National and Kapodistrian University of Athens
• Contact: Anastasios Apostolos, MD, PhD
• Phone: 6980870458
• Email: anastasisapostolos[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 1, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Device:
• Percutaneous Patent Foramen Ovale Closure
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.

Locations

Country	Name	City	State
Greece	First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens	Athens	Attica

Sponsors (1)

Lead Sponsor	Collaborator
National and Kapodistrian University of Athens

Country where clinical trial is conducted

Greece, 

References & Publications (4)

Ahlstrom MG, Thyssen JP, Wennervaldt M, Menne T, Johansen JD. Nickel allergy and allergic contact dermatitis: A clinical review of immunology, epidemiology, exposure, and treatment. Contact Dermatitis. 2019 Oct;81(4):227-241. doi: 10.1111/cod.13327. Epub — View Citation

Apostolos A, Drakopoulou M, Toutouzas K. New migraines after atrial septal defect occlusion. Is the nickel hypersensitivity the start of everything? Med Hypotheses. 2021 Jan;146:110442. doi: 10.1016/j.mehy.2020.110442. Epub 2020 Nov 30. No abstract availa — View Citation

Prestipino F, Pragliola C, Lusini M, Chello M. Nickel allergy induced systemic reaction to an intracardiac amplatzer device. J Card Surg. 2014 May;29(3):349-50. doi: 10.1111/jocs.12331. — View Citation

Schalock PC, Crawford G, Nedorost S, Scheinman PL, Atwater AR, Mowad C, Brod B, Ehrlich A, Watsky KL, Sasseville D, Silvestri D, Worobec SM, Elliott JF, Honari G, Powell DL, Taylor J, DeKoven J. Patch Testing for Evaluation of Hypersensitivity to Implante — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Residual interatrial leakage	Evaluation of residual interatrial leakage, by performing transthoracic echocardiography	90 days after the procedure
Secondary	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
Secondary	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