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Theophylline for Low Adenosine Syncope (THEO-USA)

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ClinicalTrials.gov Identifier: NCT03803215
Recruitment Status : Recruiting
First Posted : January 14, 2019
Last Update Posted : January 14, 2019
Sponsor:
Collaborator:
Gruppo Italiano Multidisciplinare per lo Studio della Sincope
Information provided by (Responsible Party):
Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella

Brief Summary:
The study aims at assessing that theophylline is effective in patients with no prodromes, normal heart and with low values of plasmatic adenosine compared with a propensity-score matched untreated control population who have received an implantable cardiac monitor (ICM) for diagnosis of unexplained or atypical reflex syncope.

Condition or disease Intervention/treatment
Syncope Drug: Theophylline

Detailed Description:

Theophylline has been used for 3 decades in ordinary medical practice to tentatively prevent syncopal recurrences in patients affected by neurally-mediated syncope. Observational studies report a recurrence rate with this drug ranging between 12% and 22%. Theophylline was much more effective in selected patients with syncope without prodromes and normal heart who had ECG documentation of long pauses at the time of syncopal attack and low values of baseline plasmatic adenosine. Since theophylline is a non-selective antagonist of purinergic receptors, it has been hypothesized that purinergic receptors are involved in the mechanism of syncope in such patients. Conversely, theophylline was suspected to be ineffective (or less effective) in patients affected by other forms of neurally-mediated syncope.

The present study aims at assessing that theophylline is effective in patients with no prodromes, normal heart and with low values of plasmatic adenosine compared with a propensity-score matched untreated control population.

This will be a multicenter, non interventional study, verified by ICM, with 2 predefined subgroups:

Subgroup #1

  • Low adenosine group: Patients with Low Adenosine values (<0.40 μmol/L)
  • Normal/high adenosine (≥0.40 μmol/L) group: any other patient Subgroup #2
  • Patients with no prodromes or very short prodromes (≤5 sec), normal heart and normal ECG (No prodrome group)
  • Any other form of atypical neurally-mediated syncope with prodromes >5 sec. Remote or in-hospital periodic follow-up will be done according to centre's clinical practice for ICM monitoring.

Patients will be followed up until the first primary endpoint event with a maximum follow-up of 24 months since start of theophylline treatment.


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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Theophylline in Patients With Unexplained Syncope and Low Adenosine. Study Verified by ICM, Controlled by Propensity-score Matching
Actual Study Start Date : May 11, 2016
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Theophylline group
Patients who have electrocardiographic documentation of asystolic syncope will be treated with oral theophylline at tailored dosage
Drug: Theophylline
Oral theophylline initially 600 mg bid and then titrated at the maximum tolerated dose

Control untreated group
A propensity-score matched control group is generated from the large database of patients who had received an implantable loop recorder



Primary Outcome Measures :
  1. Asystolic syncope [ Time Frame: 24 months ]
    Number of patients. The primary objective aims to test the hypothesis that theophylline is able to reduce asystolic events in the Low-Adenosine subgroup compared with the propensity-score matched control group


Secondary Outcome Measures :
  1. Time to first syncope recurrence [ Time Frame: 24 months ]
    Months from enrolment to the first recurrence of syncope

  2. Asystolic syncope in the subgroup with low adenosine plasmatic values [ Time Frame: 24 months ]
    Number of patients with asystolic syncope during follow-up

  3. Asystolic syncope in patients without prodrome, normal heart and normal ECG [ Time Frame: 24 months ]
    Number of patients with asystolic syncope during follow-up



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients who have received an implantable cardiac monitor (ICM) for diagnosis of unexplained or atypical reflex syncope
Criteria

Inclusion Criteria:

  1. Male or female gender with age >18 years
  2. Unexplained syncope without prodrome or neurally-mediated syncope with atypical prodrome, with normal heart and normal ECG
  3. Two syncopes /last year or 3 syncopes /last 2 years before start of theophylline treatment
  4. Having received an ICM according to conventional guideline-based indications
  5. Being treated with oral theophylline therapy, while been waiting for ICM diagnosis
  6. Having signed a written informed consent to the study participation and to the treatment of personal data

Exclusion Criteria:

  1. Typical vaso-vagal syncope with long prodromes and situational syncope
  2. Any other form of syncope/T-LOC different from reflex syncope
  3. Pregnant or breast-feeding patients -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03803215


Contacts
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Contact: Michele Brignole, MD +390185329567 mbrignole@ASL4.liguria.it

Locations
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Italy
Department of Cardiology, Ospedali del Tigullio Recruiting
Lavagna, Italy, 16033
Contact: Michele Brignole, MD    0185329567    mbrignole@asl4.liguria.it   
Sponsors and Collaborators
Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella
Gruppo Italiano Multidisciplinare per lo Studio della Sincope
Investigators
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Principal Investigator: Michele Brignole, MD Department of Cardiology, Ospedali del Tigullio

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Responsible Party: Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella
ClinicalTrials.gov Identifier: NCT03803215     History of Changes
Other Study ID Numbers: CPM 30102018
First Posted: January 14, 2019    Key Record Dates
Last Update Posted: January 14, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella:
theophylline
asystole
implantable loop recorder
Additional relevant MeSH terms:
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Adenosine
Syncope
Unconsciousness
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Theophylline
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Anti-Asthmatic Agents
Respiratory System Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists