Sinus BradycardiaPhase 1NCT02462941
Analysis of Adenosine on Sinus and Atrioventricular Nodal Conduction in the Pediatric Transplanted Heart
A Phase 1 study testing Adenosine and Cardiac catheterization in people with Sinus Bradycardia and Atrioventricular Block, run by Columbia University at 1 site in United States.
Trial summary
Heart transplants save the lives of nearly 500 children in heart failure per year. Columbia is one of the largest pediatric heart transplant centers in the world, averaging 25 transplants per year, and providing ongoing care to nearly 250 children with transplanted hearts. Read more about this study
- Who is it for?
- Ages 6 months to 25 years
- Conditions the study is for
- Sinus Bradycardia, Atrioventricular Block
- What is being tested?
- Adenosine and Cardiac catheterization
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to Jul 2017
- Phase
- Phase 1
- 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 6 months to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients who have undergone a heart transplantation and who receive their routine care at the Morgan Stanley Children's Hospital of New York, Columbia University Medical Center
Who cannot join
- Patients admitted to the inpatient heart failure team
- Patients present for their first outpatient catheterization after new transplant
- Abnormal hemodynamics concerning for acute rejection
- Patients present for follow up of rejection (last biopsy positive)
- Ingested methylxanthine-containing foods that day
- Patients taking oral dipyridamole and did not discontinue it 3 days prior to testing
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- Prior transplant history of coronary artery vasculopathy with this allograft or concern for abnormal coronary vasculature by angiography on the day of the catheterization
- Patients taking carbamazepine (may potentiate adenosine effect)
- Patients with known conduction disease (first, second or third degree atrioventricular block) and/or with pre-existing sinus node dysfunction (based on pre-existing ECG, Holter or inpatient telemetry)
- Patients/guardians unable to give consent in English
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: Prospective Analysis of Low-Dose Adenosine on Sinus and Atrioventricular Nodal Conduction in the Pediatric Transplanted Heart
Heart transplants save the lives of nearly 500 children in heart failure per year. Columbia is one of the largest pediatric heart transplant centers in the world, averaging 25 transplants per year, and providing ongoing care to nearly 250 children with transplanted hearts. After transplant, children are at increased risk to develop sudden onset of abnormally fast heart rates. This research project will study adenosine, a medication that is routinely used to slow fast heart rates in non-transplanted children (i.e. normal hearts), and its effects on the transplanted heart. Adenosine is often not used in patients with transplanted hearts because, based on prior limited research in adult patients, the standard adult dose may have a longer medication effect, producing a slower heart rate for an undesirable period of time. However, the current alternatives to adenosine treatment are either inappropriate for the pediatric age range, or have increased risk of unwanted side effects. This research project will answer two questions: is adenosine safe to give a child who has had a heart transplant, and will it be effective in treating the fast heart rate?
All pediatric heart transplant patients undergo regular heart testing, known as a cardiac catheterization, one or more times per year. Three days before testing, participants will be asked to stop a regular medication, dipyridamole, because it slows the breakdown of adenosine in the body, and may increase its effects. (Of note, all patients that are on dipyridamole are also on aspirin, which gives a second line of heart protection, and will not be stopped.) After regular cardiac catheterization, all patients will already have intravenous (IV) access to give medication. Also, this setting allows the opportunity to have a back-up pacing catheter in the heart, ensuring that there will not be a longer than desired effect from the medication. Adenosine will be given per a low-dose protocol until either the medication effect is seen or the maximum dose is reached. There will be no difference in procedure recovery period time, and patients will resume regular home medications after finishing the test. As Columbia is one of largest pediatric heart transplant centers in the world, studying the effects of adenosine at low doses will benefit the investigators population greatly, either to find a new recommended medication dose, or to provide evidence that this medication is truly inadvisable for the investigators patients.
The initial study was completed with all 80 patients enrolled and tested. Subsequent testing is now ongoing on patients in whom dipyridamole was stopped prior to their initial testing with a repeat study without discontinuing the dipyridamole. We anticipate re-testing about 30 of the 80 patients.
Read the detailed description
After cardiac catheterization, the study protocol will begin with 12.5µg/kg of adenosine (one eighth the recommended starting clinical dose), and will double to 25µg/kg, 50µg/kg, 100µg/kg and finally 200µg/kg (not to surpass the total maximum dose of 12mg). A pacing catheter will be placed within the right ventricle prior to medication administration. Escalating doses will stop if ventricular pacing is required due to a ventricular pause greater than 12 seconds or if atrioventricular block is demonstrated with a ventricular pause less than 12 seconds. If there is no prolonged pause requiring pacing and no demonstration of medication effect the subsequent dose will be given.
Progression to the next dose of the adenosine will depend on both the primary and secondary study outcomes. If the adenosine dose produces clinically significant bradycardia (> 12 seconds), ventricular pacing will be used to maintain cardiac output, and the dose will be considered unsafe to use clinically and testing will end for that patient. If the adenosine dose produces atrioventricular block but with a pause of less than 12 seconds (thus does not require pacing), the dose will be considered effective and the study will terminate as well. However, if the adenosine dose does not produce atrioventricular block or require pacing intervention, the dose will be considered safe but ineffective and the study will progress to the next higher dose. Before dose progression, the study will pause for additional 30 seconds to ensure complete adenosine metabolism, as the half-life of adenosine is less than 10 seconds and does not exhibit cumulative effects. The subsequent dose will then be administered and the ECG observed for clinically significant bradycardia and atrioventricular block. This will be repeated until clinically significant bradycardia and/or atrioventricular block is observed, or up to the final 200μg/kg (not to surpass the total maximum of 12mg) dose.
The same study protocol is being utilized to retest the subset of patients in whom dipyridamole was discontinued prior to the initial testing to further understand the safety of administering adenosine to heart transplant patients chronically maintained on dipyridamole.
- Conditions
- Sinus Bradycardia, Atrioventricular Block
- Being tested
- Adenosine, Cardiac catheterization
- Keywords
- Heart transplant, Adenosine, Pediatrics
- Medical subject headings
- Atrioventricular Block
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdenosineDrug
Also called No brand names
Testing escalating doses of adenosine in pediatric heart transplant patients
Cardiac catheterizationProcedure or surgery
(non-experimental) standard procedure
| Study group | Role | What they receive |
|---|---|---|
| Adenosine | Experimental | After cardiac catheterization, the study protocol will begin with 12.5µg/kg of adenosine (one eighth the recommended starting clinical dose), and will double to 25µg/kg, 50µg/kg, 100µg/kg and finally 200µg/kg (not to surpass the total maximum dose of 12mg). A pacing catheter will be placed within the right ventricle prior to medication administration. Escalating doses will stop if ventricular pacing is required due to a ventricular pause greater than 12 seconds or if atrioventricular block is demonstrated with a ventricular pause less than 12 seconds. If there is no prolonged pause requiring pacing and no demonstration of medication effect the subsequent dose will be given. Receives: Drug: Adenosine; Procedure: Cardiac catheterization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of sinus bradycardia or atrioventricular block with low-dose adenosine administration that is greater than 12 seconds and requires hemodynamic intervention (ventricular escape pacing).
Measured: Up to 1 hour after the catheterization
Secondary outcomes (1)
Prevalence of inducing atrioventricular block (defined as a single non-conducted P wave) at adenosine doses lower than suggested starting dose (100µg/kg) in PALS algorithm.
Measured: Up to 1 hour after the catheterization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2015 (estimated)
- Study startJul 2015
- Primary completionApr 2016
- Study completionJul 2017
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 Sinus BradycardiaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eric Silver, Columbia University
- Investigators
- Eric S Silver, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02462941
- Sponsor's protocol ID
- AAAO8054
- Status last verified
- Feb 2018
- First submitted
- 26 Feb 2015
- Last updated
- 8 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Flyer JN, Zuckerman WA, Richmond ME, Anderson BR, Mendelsberg TG, McAllister JM, Liberman L, Addonizio LJ, Silver ES. Prospective Study of Adenosine on Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After Heart Transplantation. Circulation. 2017 Jun 20;135(25):2485-2493. doi: 10.1161/CIRCULATIONAHA.117.028087. Epub 2017 Apr 27.
PubMed 28450351
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Analysis of Low-Dose Adenosine on Sinus and Atrioventricular Nodal Conduction in the Pediatric Transplanted Heart
- ClinicalTrials.gov ID
- NCT02462941
- Acronym / sponsor ID
- AAAO8054
- Conditions
- Sinus Bradycardia, Atrioventricular Block
- Keywords
- Heart transplant, Adenosine, Pediatrics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 4 Jun 2015 (estimated)
- 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.
Heart transplants save the lives of nearly 500 children in heart failure per year. Columbia is one of the largest pediatric heart transplant centers in the world, averaging 25 transplants per year, and providing ongoing care to nearly 250 children with transplanted hearts. After transplant, children are at increased risk to develop sudden onset of abnormally fast heart rates. This research project will study adenosine, a medication that is routinely used to slow fast heart rates in non-transplanted children (i.e. normal hearts), and its effects on the transplanted heart. Adenosine is often not used in patients with transplanted hearts because, based on prior limited research in adult patients, the standard adult dose may have a longer medication effect, producing a slower heart rate for an undesirable period of time. However, the current alternatives to adenosine treatment are either inappropriate for the pediatric age range, or have increased risk of unwanted side effects. This research project will answer two questions: is adenosine safe to give a child who has had a heart transplant, and will it be effective in treating the fast heart rate?
All pediatric heart transplant patients undergo regular heart testing, known as a cardiac catheterization, one or more times per year. Three days before testing, participants will be asked to stop a regular medication, dipyridamole, because it slows the breakdown of adenosine in the body, and may increase its effects. (Of note, all patients that are on dipyridamole are also on aspirin, which gives a second line of heart protection, and will not be stopped.) After regular cardiac catheterization, all patients will already have intravenous (IV) access to give medication. Also, this setting allows the opportunity to have a back-up pacing catheter in the heart, ensuring that there will not be a longer than desired effect from the medication. Adenosine will be given per a low-dose protocol until either the medication effect is seen or the maximum dose is reached. There will be no difference in procedure recovery period time, and patients will resume regular home medications after finishing the test. As Columbia is one of largest pediatric heart transplant centers in the world, studying the effects of adenosine at low doses will benefit the investigators population greatly, either to find a new recommended medication dose, or to provide evidence that this medication is truly inadvisable for the investigators patients.
The initial study was completed with all 80 patients enrolled and tested. Subsequent testing is now ongoing on patients in whom dipyridamole was stopped prior to their initial testing with a repeat study without discontinuing the dipyridamole. We anticipate re-testing about 30 of the 80 patients.
Detailed description
After cardiac catheterization, the study protocol will begin with 12.5µg/kg of adenosine (one eighth the recommended starting clinical dose), and will double to 25µg/kg, 50µg/kg, 100µg/kg and finally 200µg/kg (not to surpass the total maximum dose of 12mg). A pacing catheter will be placed within the right ventricle prior to medication administration. Escalating doses will stop if ventricular pacing is required due to a ventricular pause greater than 12 seconds or if atrioventricular block is demonstrated with a ventricular pause less than 12 seconds. If there is no prolonged pause requiring pacing and no demonstration of medication effect the subsequent dose will be given.
Progression to the next dose of the adenosine will depend on both the primary and secondary study outcomes. If the adenosine dose produces clinically significant bradycardia (> 12 seconds), ventricular pacing will be used to maintain cardiac output, and the dose will be considered unsafe to use clinically and testing will end for that patient. If the adenosine dose produces atrioventricular block but with a pause of less than 12 seconds (thus does not require pacing), the dose will be considered effective and the study will terminate as well. However, if the adenosine dose does not produce atrioventricular block or require pacing intervention, the dose will be considered safe but ineffective and the study will progress to the next higher dose. Before dose progression, the study will pause for additional 30 seconds to ensure complete adenosine metabolism, as the half-life of adenosine is less than 10 seconds and does not exhibit cumulative effects. The subsequent dose will then be administered and the ECG observed for clinically significant bradycardia and atrioventricular block. This will be repeated until clinically significant bradycardia and/or atrioventricular block is observed, or up to the final 200μg/kg (not to surpass the total maximum of 12mg) dose.
The same study protocol is being utilized to retest the subset of patients in whom dipyridamole was discontinued prior to the initial testing to further understand the safety of administering adenosine to heart transplant patients chronically maintained on dipyridamole.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adenosine | Experimental | Drug: Adenosine, Procedure: Cardiac catheterizationAfter cardiac catheterization, the study protocol will begin with 12.5µg/kg of adenosine (one eighth the recommended starting clinical dose), and will double to 25µg/kg, 50µg/kg, 100µg/kg and finally 200µg/kg (not to surpass the total maximum dose of 12mg). A pacing catheter will be placed within the right ventricle prior to medication administration. Escalating doses will stop if ventricular pacing is required due to a ventricular pause greater than 12 seconds or if atrioventricular block is demonstrated with a ventricular pause less than 12 seconds. If there is no prolonged pause requiring pacing and no demonstration of medication effect the subsequent dose will be given. |
Who may qualify
- Ages
- 6 months to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Patients who have undergone a heart transplantation and who receive their routine care at the Morgan Stanley Children's Hospital of New York, Columbia University Medical Center
Key exclusion criteria (10 listed)
- Patients admitted to the inpatient heart failure team
- Patients present for their first outpatient catheterization after new transplant
- Abnormal hemodynamics concerning for acute rejection
- Patients present for follow up of rejection (last biopsy positive)
- Ingested methylxanthine-containing foods that day
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 |
|---|---|---|
| AdenosineAlso: No brand namesTesting escalating doses of adenosine in pediatric heart transplant patients | Drug | Adenosine |
| Cardiac catheterization(non-experimental) standard procedure | Procedure or surgery | Adenosine |
Primary outcome
Incidence of sinus bradycardia or atrioventricular block with low-dose adenosine administration that is greater than 12 seconds and requires hemodynamic intervention (ventricular escape pacing).
Time frame: Up to 1 hour after the catheterization
1 secondary outcome
Prevalence of inducing atrioventricular block (defined as a single non-conducted P wave) at adenosine doses lower than suggested starting dose (100µg/kg) in PALS algorithm.
Time frame: Up to 1 hour after the catheterization
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 8 Feb 2018.
- Derived from this study: PubMed 28450351Flyer JN, Zuckerman WA, Richmond ME, Anderson BR, Mendelsberg TG, McAllister JM, Liberman L, Addonizio LJ, Silver ES. Prospective Study of Adenosine on Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After Heart Transplantation. Circulation. 2017 Jun 20;135(25):2485-2493. doi: 10.1161/CIRCULATIONAHA.117.028087. Epub 2017 Apr 27.
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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.
Eric S Silver, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Adenosine and Cardiac catheterization in people with Sinus Bradycardia and Atrioventricular Block, run by Columbia University at 1 site in United States.
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 1 inclusion and 10 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 8 Feb 2018. 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 United States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Incidence of sinus bradycardia or atrioventricular block with low-dose adenosine administration that is greater than 12 seconds and requires hemodynamic intervention (ventricular escape pacing). (time frame: Up to 1 hour after the catheterization). 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 NCT02462941, 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 8 Feb 2018.