SyncopeTHEO-USANCT03803215
Theophylline for Low Adenosine Syncope
An observational study of Syncope, run by Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Syncope
- What is being tested?
- Theophylline
- Type of treatment
- Pill or oral medicine
- How many people
- 77 participants
- Where
- 1 siteItaly
- Study dates
- 11 May 2016to 30 Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients who have received an implantable cardiac monitor (ICM) for diagnosis of unexplained or atypical reflex syncope
Who may be able to join
- Male or female gender with age >18 years
- Unexplained syncope without prodrome or neurally-mediated syncope with atypical prodrome, with normal heart and normal ECG
- Two syncopes /last year or 3 syncopes /last 2 years before start of theophylline treatment
- Having received an ICM according to conventional guideline-based indications
- Being treated with oral theophylline therapy, while been waiting for ICM diagnosis
- Having signed a written informed consent to the study participation and to the treatment of personal data
Who cannot join
- Typical vaso-vagal syncope with long prodromes and situational syncope
- Any other form of syncope/T-LOC different from reflex syncope
- Pregnant or breast-feeding patients -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Theophylline in Patients With Unexplained Syncope and Low Adenosine. Study Verified by ICM, Controlled by Propensity-score Matching
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.
Read the 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.
- Conditions
- Syncope
- Being tested
- Theophylline
- Keywords
- theophylline, asystole, implantable loop recorder
- Medical subject headings
- Syncope, Heart Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TheophyllineDrug
Oral theophylline initially 600 mg bid and then titrated at the maximum tolerated dose
| Study group | Role | What they receive |
|---|---|---|
| Theophylline group | Patients who have electrocardiographic documentation of asystolic syncope will be treated with oral theophylline at tailored dosage Receives: Drug: Theophylline | |
| Control untreated group | A propensity-score matched control group is generated from the large database of patients who had received an implantable loop recorder |
What is being measured
The primary outcome is the main question the study is designed to answer.
Asystolic syncope
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
Measured: 24 months
Secondary outcomes (3)
Time to first syncope recurrence
Months from enrolment to the first recurrence of syncope
Measured: 24 months
Asystolic syncope in the subgroup with low adenosine plasmatic values
Number of patients with asystolic syncope during follow-up
Measured: 24 months
Asystolic syncope in patients without prodrome, normal heart and normal ECG
Number of patients with asystolic syncope during follow-up
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2019
- Study start11 May 2016
- Primary completion30 Nov 2020
- Study completion30 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SyncopeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella
- Sponsor type
- University, hospital or other
- Collaborators
- Gruppo Italiano Multidisciplinare per lo Studio della Sincope
- Responsible party
- Sponsor
- Investigators
- Michele Brignole, MD, Principal investigator, Department of Cardiology, Ospedali del Tigullio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03803215
- Sponsor's protocol ID
- CPM 30102018
- Acronym
- THEO-USA
- Status last verified
- Jan 2020
- First submitted
- 10 Jan 2019
- Last updated
- 20 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Brignole M, Iori M, Strano S, Tomaino M, Rivasi G, Ungar A, Carretta D, Solari D, Napoli P, Deharo JC, Guieu R. Theophylline in patients with syncope without prodrome, normal heart, and normal electrocardiogram: a propensity-score matched study verified by implantable cardiac monitor. Europace. 2022 Jul 21;24(7):1164-1170. doi: 10.1093/europace/euab300.
PubMed 34849728
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Theophylline in Patients With Unexplained Syncope and Low Adenosine. Study Verified by ICM, Controlled by Propensity-score Matching
- ClinicalTrials.gov ID
- NCT03803215
- Acronym / sponsor ID
- THEO-USA / CPM 30102018
- Conditions
- Syncope
- Keywords
- theophylline, asystole, implantable loop recorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Centro Prevenzione Malattie Cardiovascolari N. e V. CorbellaUniversity, hospital or other
- Collaborators
- Gruppo Italiano Multidisciplinare per lo Studio della Sincope
- Study start
- 11 May 2016 (actual)
- Primary completion
- 30 Nov 2020 (actual)
- Study completion
- 30 Dec 2020 (actual)
- First posted
- 14 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Theophylline group | – | Drug: TheophyllinePatients who have electrocardiographic documentation of asystolic syncope will be treated with oral theophylline at tailored dosage |
| Control untreated group | – | –A propensity-score matched control group is generated from the large database of patients who had received an implantable loop recorder |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who have received an implantable cardiac monitor (ICM) for diagnosis of unexplained or atypical reflex syncope
Key inclusion criteria (6 listed)
- Male or female gender with age >18 years
- Unexplained syncope without prodrome or neurally-mediated syncope with atypical prodrome, with normal heart and normal ECG
- Two syncopes /last year or 3 syncopes /last 2 years before start of theophylline treatment
- Having received an ICM according to conventional guideline-based indications
- Being treated with oral theophylline therapy, while been waiting for ICM diagnosis
Key exclusion criteria (3 listed)
- Typical vaso-vagal syncope with long prodromes and situational syncope
- Any other form of syncope/T-LOC different from reflex syncope
- Pregnant or breast-feeding patients -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TheophyllineOral theophylline initially 600 mg bid and then titrated at the maximum tolerated dose | Drug | Theophylline group |
Primary outcome
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
3 secondary outcomes
Time to first syncope recurrence
Time frame: 24 months
Asystolic syncope in the subgroup with low adenosine plasmatic values
Time frame: 24 months
Asystolic syncope in patients without prodrome, normal heart and normal ECG
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2021.
- Derived from this study: PubMed 34849728Brignole M, Iori M, Strano S, Tomaino M, Rivasi G, Ungar A, Carretta D, Solari D, Napoli P, Deharo JC, Guieu R. Theophylline in patients with syncope without prodrome, normal heart, and normal electrocardiogram: a propensity-score matched study verified by implantable cardiac monitor. Europace. 2022 Jul 21;24(7):1164-1170. doi: 10.1093/europace/euab300.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michele Brignole, MD principal investigator
Department of Cardiology, Ospedali del Tigullio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Syncope, run by Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Asystolic syncope (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03803215, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2021; AzTrials last refreshed its copy on 27 Oct 2026.