Atrial FibrillationPhase 2DREAMNCT02099331
Cardiac Surgery and the Risk of Atrial Fibrillation: an Intervention Trial Evaluating Melatonin
A Phase 2 study testing Melatonin in people with Atrial Fibrillation, run by Johns Hopkins University at 1 site in United States.
Trial summary
Atrial fibrillation is a common heart rhythm condition that can occur after cardiac surgery and has been associated with an increase in hospital length of stay, overall hospital costs, worsening clinical condition and higher rates of death. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to 6 Jul 2015
- Phase
- Phase 2
- 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
Who may be able to join
- Age over the age of 18.
- Scheduled for elective cardiac surgery (coronary artery bypass grafting, valvular surgery or combined procedures)
- Enroll at least 48 hours before surgery is scheduled
- Presence of normal sinus rhythm on screening electrocardiogram.
- Be willing to provide informed consent (which may be provided by a legally authorized representative if the patient is not able to do so).
Who cannot join
- History of prior atrial fibrillation
- Inability to give informed consent.
- Use of anti-arrhythmic drugs other than beta-blockers
- Chronic NSAID or antioxidant use
- History of severe autoimmune disorders with the need for autoimmune medications.
- History of epilepsy.
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- Compromised hepatic function (aminotransferase levels > 1.5 times the upper limit of normal)
- Current pregnancy (determined by either serum or urine pregnancy test, as ordered by the primary team)
- Non-English Speakers
- Current use of warfarin, nifedipine, fluvoxamine.
Trial locations and contacts
1 site in 1 country.
About this study
Atrial fibrillation is a common heart rhythm condition that can occur after cardiac surgery and has been associated with an increase in hospital length of stay, overall hospital costs, worsening clinical condition and higher rates of death. Newer research indicates that inflammation is a key contributor to atrial fibrillation in this setting.
Melatonin is a naturally made hormone that is regarded as an extremely effective anti-inflammatory substance, with a very favorable safety profile. This clinical trial is being done to test the ability of melatonin to reduce the risk of developing atrial fibrillation after cardiac surgery.
Read more
This is a research study where patients will be given either oral melatonin at 40 mg or placebo nightly prior to sleep. The study product will start approximately 2 days prior to the scheduled surgery date and will continue until the 3rd day after the operation. The remainder of the clinical care will remain the same.
The investigators project that patients who receive melatonin will have a significant decrease in the occurrence of atrial fibrillation after surgery.
Read the detailed description
Atrial fibrillation is the most common arrhythmia to occur after coronary artery bypass graft (CABG) surgery. This arrhythmia occurs in approximately 1 in every 3 patients in this setting and the rate is even higher after valve or combined valve and CABG procedures. The majority of episodes of atrial fibrillation occur within the first 3 days after cardiac surgery and for those who have an initial episode of atrial fibrillation, the majority will go on to have another recurrence within 2 days of the first episode. Postoperative atrial fibrillation has been associated with an increase in neurological, renal and infectious complications as well as prolonged hospitalization and a significant increase in overall healthcare costs.
There is a considerable amount of emerging data indicating that inflammation and oxidative stress, by way of reactive oxygen species (ROS), associated with cardiac surgery and cardiopulmonary bypass (CPB) may play an important role in the in the development of postoperative atrial fibrillation. Prior animal studies have demonstrated that ROS may lead to electroanatomical remodeling and increase the vulnerability to atrial fibrillation by promoting progressive fibrosis and subsequent alteration of the extracellular matrix. A few randomized controlled trials have demonstrated the beneficial effects of pre-treatment with anti-inflammatory medications such as statins for the prevention of post-operative atrial fibrillation. With this in mind, other anti-inflammatory therapies may also be effective in preventing postoperative atrial fibrillation.
Melatonin (N - acetyl - 5 - methoxytryptamine) is the main product secreted from the pineal gland and has been shown to be a powerful scavenger of ROS and is regarded as the most potent endogenous antioxidant. In fact, melatonin is more effective than other antioxidants in removing free radicals and it has both lipophilic and hydrophilic properties contributing to its more consistent penetration through cellular membranes. In addition to being a naturally synthesized hormone, melatonin has been shown to have a very favorable safety profile when administered in the clinical setting.
For these reasons, investigators have designed a randomized, double-blind, placebo-controlled trial where patients who are to undergo cardiac surgery and CPB, will be randomized to melatonin or placebo and the investigators will determine the incidence of post operative atrial fibrillation in both groups. Additionally, the investigators will measure ROS from serum as well as right atrial appendage samples of subjects and assess the effects of melatonin on ROS levels as compared to placebo.
- Conditions
- Atrial Fibrillation
- Being tested
- Melatonin, Placebo (for Melatonin)
- Keywords
- Atrial Fibrillation, Reactive Oxygen Species, Cardiac Surgery
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Also called N - acetyl - 5 - methoxytryptamine
Placebo (for Melatonin)Drug
Sugar pill manufactured to mimic Melatonin 20 mg
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Experimental | The investigators will administer melatonin at 40mg by mouth (two 20 mg tablets), nightly prior to sleep. The administration will start 2 days prior to the scheduled surgery date and will continue until post-operative day 3. Receives: Drug: Melatonin |
| Placebo | Placebo comparator | The investigators will administer matching Placebo by mouth (two tablets to match Melatonin), nightly prior to sleep. The administration will start 2 days prior to the scheduled surgery date and will continue until post-operative day 3. Receives: Drug: Placebo (for Melatonin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of atrial fibrillation
At the end of the study, the primary outcome of incident atrial fibrillation will be assessed in each study arm.
Measured: 2 years
Secondary outcomes (1)
Levels of Reactive Oxygen Species (ROS)
The investigators will measure levels of ROS from the right atrial appendage and serum samples at the time of surgery as well as on a daily basis from the serum for three days after surgery. Specifically, the investigators will measure NADPH oxidase, peroxide anion, peroxynitrite and thiobarbituric acid reactive substances. At the end of the study, the investigators will compare these levels in both arms.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2014 (estimated)
- Study startSep 2014
- Primary completion6 Jul 2015
- Study completion6 Jul 2015
Why it stopped: Lack of faculty staffing
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Johns Hopkins 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Oscar Cingolani, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02099331
- Sponsor's protocol ID
- NA_00090647
- Acronym
- DREAM
- Status last verified
- Aug 2021
- First submitted
- 22 Mar 2014
- Last updated
- 12 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Surgery and the Risk of Atrial Fibrillation: an Intervention Trial Evaluating Melatonin
- ClinicalTrials.gov ID
- NCT02099331
- Acronym / sponsor ID
- DREAM / NA_00090647
- Conditions
- Atrial Fibrillation
- Keywords
- Atrial Fibrillation, Reactive Oxygen Species, Cardiac Surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of faculty staffing
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- 6 Jul 2015 (actual)
- Study completion
- 6 Jul 2015 (actual)
- First posted
- 28 Mar 2014 (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.
Atrial fibrillation is a common heart rhythm condition that can occur after cardiac surgery and has been associated with an increase in hospital length of stay, overall hospital costs, worsening clinical condition and higher rates of death. Newer research indicates that inflammation is a key contributor to atrial fibrillation in this setting.
Melatonin is a naturally made hormone that is regarded as an extremely effective anti-inflammatory substance, with a very favorable safety profile. This clinical trial is being done to test the ability of melatonin to reduce the risk of developing atrial fibrillation after cardiac surgery.
This is a research study where patients will be given either oral melatonin at 40 mg or placebo nightly prior to sleep. The study product will start approximately 2 days prior to the scheduled surgery date and will continue until the 3rd day after the operation. The remainder of the clinical care will remain the same.
The investigators project that patients who receive melatonin will have a significant decrease in the occurrence of atrial fibrillation after surgery.
Detailed description
Atrial fibrillation is the most common arrhythmia to occur after coronary artery bypass graft (CABG) surgery. This arrhythmia occurs in approximately 1 in every 3 patients in this setting and the rate is even higher after valve or combined valve and CABG procedures. The majority of episodes of atrial fibrillation occur within the first 3 days after cardiac surgery and for those who have an initial episode of atrial fibrillation, the majority will go on to have another recurrence within 2 days of the first episode. Postoperative atrial fibrillation has been associated with an increase in neurological, renal and infectious complications as well as prolonged hospitalization and a significant increase in overall healthcare costs.
There is a considerable amount of emerging data indicating that inflammation and oxidative stress, by way of reactive oxygen species (ROS), associated with cardiac surgery and cardiopulmonary bypass (CPB) may play an important role in the in the development of postoperative atrial fibrillation. Prior animal studies have demonstrated that ROS may lead to electroanatomical remodeling and increase the vulnerability to atrial fibrillation by promoting progressive fibrosis and subsequent alteration of the extracellular matrix. A few randomized controlled trials have demonstrated the beneficial effects of pre-treatment with anti-inflammatory medications such as statins for the prevention of post-operative atrial fibrillation. With this in mind, other anti-inflammatory therapies may also be effective in preventing postoperative atrial fibrillation.
Melatonin (N - acetyl - 5 - methoxytryptamine) is the main product secreted from the pineal gland and has been shown to be a powerful scavenger of ROS and is regarded as the most potent endogenous antioxidant. In fact, melatonin is more effective than other antioxidants in removing free radicals and it has both lipophilic and hydrophilic properties contributing to its more consistent penetration through cellular membranes. In addition to being a naturally synthesized hormone, melatonin has been shown to have a very favorable safety profile when administered in the clinical setting.
For these reasons, investigators have designed a randomized, double-blind, placebo-controlled trial where patients who are to undergo cardiac surgery and CPB, will be randomized to melatonin or placebo and the investigators will determine the incidence of post operative atrial fibrillation in both groups. Additionally, the investigators will measure ROS from serum as well as right atrial appendage samples of subjects and assess the effects of melatonin on ROS levels as compared to placebo.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Experimental | Drug: MelatoninThe investigators will administer melatonin at 40mg by mouth (two 20 mg tablets), nightly prior to sleep. The administration will start 2 days prior to the scheduled surgery date and will continue until post-operative day 3. |
| Placebo | Placebo comparator | Drug: Placebo (for Melatonin)The investigators will administer matching Placebo by mouth (two tablets to match Melatonin), nightly prior to sleep. The administration will start 2 days prior to the scheduled surgery date and will continue until post-operative day 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age over the age of 18.
- Scheduled for elective cardiac surgery (coronary artery bypass grafting, valvular surgery or combined procedures)
- Enroll at least 48 hours before surgery is scheduled
- Presence of normal sinus rhythm on screening electrocardiogram.
- Be willing to provide informed consent (which may be provided by a legally authorized representative if the patient is not able to do so).
Key exclusion criteria (10 listed)
- History of prior atrial fibrillation
- Inability to give informed consent.
- Use of anti-arrhythmic drugs other than beta-blockers
- Chronic NSAID or antioxidant use
- History of severe autoimmune disorders with the need for autoimmune medications.
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 |
|---|---|---|
| MelatoninAlso: N - acetyl - 5 - methoxytryptamine | Drug | Melatonin |
| Placebo (for Melatonin)Sugar pill manufactured to mimic Melatonin 20 mg | Drug | Placebo |
Primary outcome
Incidence of atrial fibrillation
Time frame: 2 years
At the end of the study, the primary outcome of incident atrial fibrillation will be assessed in each study arm.
1 secondary outcome
Levels of Reactive Oxygen Species (ROS)
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
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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.
Oscar Cingolani, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melatonin in people with Atrial Fibrillation, run by Johns Hopkins 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 5 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: withdrawn, as of the sponsor's last update on 12 Aug 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 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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 atrial fibrillation (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Aug 2021.