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

NCT04713683 | Completed DMC FDA Device

• 1 other identifier: NICKEL-PFO TRIAL
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

patent foramen ovale; percutaneous pfo closure; Nickel Hypersensitivity; Nickel Sensitisation; device syndrome; skin patch tests

Outcome Measures

Primary Outcomes (1)

• Device syndrome, a composite endpoint consisting of patient-reported new-onset chest pain, palpitations, new-onset or worsening migraines, dyspnea, 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 Outcomes (10)

• The nickel patch tests' results change after Amplatzer Device implantation

  The first 90 days after the procedure

• The nickel patch tests' results change after Gore Device implantation

  The first 90 days after the procedure

• Residual interatrial leakage

  90 days after the procedure

• Rest allergens skin patch test results' change

  90 days after the procedure

• Nickel patch test results' change

  90 days after the procedure

Study Arms (2)

Amplatzer PFO Occluder

ACTIVE COMPARATOR

Patients randomized in this arm will be implanted with Amplatzer PFO Occluder.

Device: Percutaneous Patent Foramen Ovale Closure

Gore Cardioform Septal

ACTIVE COMPARATOR

Patients randomized in this arm will be implanted with Gore Cardioform Septal Occluder.

Device: Percutaneous Patent Foramen Ovale Closure

Interventions

Percutaneous Patent Foramen Ovale Closure DEVICE

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.

Also known as: Transcatheter PFO occlusion

Amplatzer PFO Occluder; Gore Cardioform Septal

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: at least 14 years old
• Well-documented indication for percutaneous PFO closure

You may not qualify if:

• Corticosteroid treatment
• Patient's refusal to participation

Sponsors & Collaborators

• National and Kapodistrian University of Athens: lead

Study Sites (1)

First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens

Athens, Attica, 115 28, Greece

Location

Related Publications (5)

• 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 available.

  PMID: 33303305 RESULT

• 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 2019 Jul 9.

  PMID: 31140194 RESULT

• 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 Implanted Metal Devices: A Perspective From the American Contact Dermatitis Society. Dermatitis. 2016 Sep-Oct;27(5):241-7. doi: 10.1097/DER.0000000000000210.

  PMID: 27649347 RESULT

• 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.

  PMID: 24762035 RESULT

• Apostolos A, Gregoriou S, Drakopoulou M, Trantalis G, Tsiogka A, Ktenopoulos N, Aggeli K, Stratigos A, Tsioufis K, Toutouzas K. Patent Foramen Ovale Closure in Patients With and Without Nickel Hypersensitivity: A Randomized Trial. Circ Cardiovasc Interv. 2025 Apr;18(4):e015228. doi: 10.1161/CIRCINTERVENTIONS.125.015228. Epub 2025 Mar 9.

  PMID: 40057986 DERIVED

MeSH Terms

Conditions

Foramen Ovale, Patent; Dermatitis, Irritant

Condition Hierarchy (Ancestors)

Heart Septal Defects, Atrial; Heart Septal Defects; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis, Contact; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous

Study Officials

• Konstantinos Toutouzas, MD,PhD

  First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens

  STUDY CHAIR

• Anastasios Apostolos, MD

  First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens

  PRINCIPAL INVESTIGATOR

• Stamatios Gregoriou, MD, PhD

  First Department of Dermatology-Venereolgy, National and Kapodistrian University of Athens, Andreas Syggros Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The dermatologist will be blinded regarding the device implanted in the patients. The interventional cardiologist will be blinded regarding the results of skin tests. The outcomes assessor will be blinded for both skin patch tests and the implanted device of each participant.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology, First Department of Cardiology, Medical School

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: January 19, 2021
• Study Start: December 10, 2020
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 6, 2025

Record last verified: 2025-02

Locations

GR (1)