Clinical trial NCT04713683: Investigation of Nickel Sensitization After Percutaneous Implantation of Patent Foramen Ovale Occluder
Official title: Investigation of Nickel Sensitization After Percutaneous Implantation of Patent Foramen Ovale Occluder; a RandomizEd Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
First posted: 2021-01-19
Enrollment: 96
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed 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.

The aim of our study is to evaluate whether patients with nickel hypersensitivity have an increased risk of adverse events following PFO closure, to assess the potential influence of device selection, and to evaluate potential sensitization or desensitization in patients without or with pre-existing nickel allergy, respectively.

Nickel hypersensitivity was assessed using skin patch testing prior to the procedure. The primary endpoint was device syndrome, a composite of patient-reported symptoms (chest pain, palpitations, migraines, dyspnea, and rash). Secondary endpoints included arrhythmias, bleeding, stroke, and all-cause mortality.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Corticosteroid treatment
* Patient's refusal to participation

Primary outcomes:
measure: Device syndrome, a composite endpoint consisting of patient-reported new-onset chest pain, palpitations, new-onset or worsening migraines, dyspnea, and rash
timeFrame: The first 90 days after the procedure
Secondary outcomes:
measure: The nickel patch tests' results change after Amplatzer Device implantation
timeFrame: The first 90 days after the procedure
measure: The nickel patch tests' results change after Gore Device implantation
timeFrame: The first 90 days after the procedure
measure: Residual interatrial leakage
timeFrame: 90 days after the procedure
measure: Rest allergens skin patch test results' change
timeFrame: 90 days after the procedure
measure: Nickel patch test results' change
timeFrame: 90 days after the procedure
measure: patient-reported new-onset chest pain
timeFrame: 90 days after the procedure
measure: palpitations
timeFrame: 90 days after the procedure
measure: new-onset or worsening migraines
timeFrame: 90 days after the procedure
measure: dyspnea
timeFrame: 90 days after the procedure
measure: Atrial arrhythmias
timeFrame: 90 days after the procedure
Other outcomes:
Locations:
city: Athens
country: Greece
facility: First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens
state: Attica
Study officials:
affiliation: First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens
name: Konstantinos Toutouzas, MD,PhD
role: STUDY_CHAIR
affiliation: First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens
name: Anastasios Apostolos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: First Department of Dermatology-Venereolgy, National and Kapodistrian University of Athens, Andreas Syggros Hospital
name: Stamatios Gregoriou, MD, PhD
role: STUDY_DIRECTOR
References:
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 available.
citation: 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.
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 Implanted Metal Devices: A Perspective From the American Contact Dermatitis Society. Dermatitis. 2016 Sep-Oct;27(5):241-7. doi: 10.1097/DER.0000000000000210.
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.