Theophylline for Low Adenosine Syncope

Completed

• Conditions: Syncope
• Interventions: Drug: Theophylline

• Registration Number: NCT03803215
• Lead Sponsor: 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.

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.

Study Timeline

• Study Start: 2016-05-11
• Study First Submitted: 2019-01-10
• Study First Submitted QC: 2019-01-11
• Study First Posted: 2019-01-14
• Status Verified: 2020-01
• Primary Completion: 2020-11-30
• Study Completion: 2020-12-30
• Last Update Submitted: 2021-01-18
• Last Update Posted: 2021-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 77

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

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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 -

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Theophylline group	Theophylline	Patients who have electrocardiographic documentation of asystolic syncope will be treated with oral theophylline at tailored dosage

Primary Outcome Measures

Name	Time	Method
Asystolic syncope	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

Name	Time	Method
Asystolic syncope in patients without prodrome, normal heart and normal ECG	24 months	Number of patients with asystolic syncope during follow-up
Asystolic syncope in the subgroup with low adenosine plasmatic values	24 months	Number of patients with asystolic syncope during follow-up
Time to first syncope recurrence	24 months	Months from enrolment to the first recurrence of syncope

Trial Locations

Locations (1)

Department of Cardiology, Ospedali del Tigullio; 🇮🇹 Lavagna, Italy