Amiodarone for Atrial Fibrillation Prevention in Esophageal Cancer Surgery

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Amiodarone

Disqualifiers: Chronic AF, Pregnancy, Breastfeeding, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 7 days

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well amiodarone works in the prevention of atrial fibrillation (AF) after a minimally invasive esophagectomy (MIE) in patients with esophageal cancer. Atrial fibrillation (AF) is an irregular heart rhythm, usually associated with a rapid rate, that is caused by abnormal electrical activity within the atria. AF is the most common complication after MIE for esophageal cancer. There has never been a study of AF after MIE that has used unbiased assignment of patients to receive preventative amiodarone or not. Further, there is no standard recommendation or guideline for preventative medications, such as amiodarone, to decrease the risk of AF in patients having MIE performed for cancer. In fact, most medical centers in the United States and around the world do not give preventative amiodarone after esophagectomy. Giving amiodarone after MIE surgery may be able to reduce the risk of AF for patients with esophageal cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking amiodarone before surgery.

What data supports the effectiveness of the drug Amiodarone for preventing atrial fibrillation after esophageal cancer surgery?

Research shows that Amiodarone is effective in preventing atrial fibrillation (a type of irregular heartbeat) after esophagectomy (surgery to remove part of the esophagus), which is a common complication that can lead to longer hospital stays and increased risk of death. ^{1 2 3 4 5}

Is amiodarone safe for humans?

Amiodarone has been studied for safety in preventing atrial fibrillation (a type of irregular heartbeat) after esophageal cancer surgery, and these studies generally focus on its use in this context. While the studies aim to assess both effectiveness and safety, they do not provide detailed safety data applicable to all conditions. ^{1 4 5 6 7}

How does the drug amiodarone differ from other treatments for preventing atrial fibrillation after esophageal cancer surgery?

Amiodarone is unique because it is used specifically to prevent atrial fibrillation (irregular heartbeat) after esophageal cancer surgery, a condition for which there are few standard treatments. It can be administered intravenously or through a nasogastric tube, which is a flexible tube inserted through the nose into the stomach, making it versatile for patients who have undergone surgery. ^{1 2 4 5 7}

Research Team

Stephanie Wood

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with esophageal cancer or related conditions who are undergoing minimally invasive esophagectomy (MIE). They must understand and consent to the study. Excluded are pregnant or breastfeeding individuals, those with certain heart rate irregularities, current amiodarone users, patients developing AF during surgery, and anyone with a history of adverse reactions to amiodarone.

Inclusion Criteria

I am older than 18 years.

I have cancer, esophageal dysplasia, or trouble swallowing.

All patients undergoing MIE will be evaluated for potential enrollment

Exclusion Criteria

My minimally invasive esophagectomy was stopped.

Women who could become pregnant must have a negative pregnancy test on the day of surgery.

I have a history of irregular heartbeats.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive amiodarone hydrochloride IV for 4 days and then via a feeding tube for 3 days, or placebo IV for 4 days

7 days

Inpatient stay during treatment

Follow-up

Participants are monitored for safety and effectiveness, including the development of atrial fibrillation and other postoperative complications

60 days

Regular follow-up visits post-discharge

Treatment Details

Interventions

• Amiodarone

Trial Overview The trial is testing if amiodarone can prevent atrial fibrillation—a common irregular heartbeat—after MIE in esophageal cancer patients. Participants will be randomly assigned to receive either amiodarone or saline as a control after their surgery to see which works better at preventing AF.

Participant Groups

Group I: Arm I (amiodarone hydrochloride) Experimental Treatment 1 Intervention

Patients receive amiodarone hydrochloride IV for 4 days and then via a feeding tube for 3 days on study.

Group II: Arm II (normal saline) Placebo Group 1 Intervention

Patients receive normal saline IV for 4 days on study.

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Findings from Research

In a study of 80 patients undergoing transthoracic esophagectomy, amiodarone significantly reduced the incidence of atrial fibrillation requiring treatment from 40% in the control group to 15%, indicating a 62.5% relative risk reduction.

The use of amiodarone did not lead to significant differences in hospital or intensive care unit stays, nor did it increase the incidence of adverse effects, suggesting it is a safe and effective prophylactic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy. Tisdale, JE., Wroblewski, HA., Wall, DS., et al.[2015]

In a study of 254 lung cancer surgery patients, postoperative amiodarone significantly reduced the incidence of atrial fibrillation, with only 11 cases in the amiodarone group compared to 38 in the placebo group (P < 0.001).

The use of amiodarone was cost-neutral, as the mean total costs per patient were similar between the amiodarone and placebo groups (€7288), and there were no adverse effects associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone is a cost-neutral way of preventing atrial fibrillation after surgery for lung cancer. Riber, LP., Christensen, TD., Pilegaard, HK.[2015]

Atrial fibrillation (AF) is more common after esophageal surgery in older male patients, particularly those with a history of chronic obstructive pulmonary disease (COPD) or cardiac disease, and is associated with postoperative hypoxia and thoracic-gastric dilatation.

Despite the increased incidence of AF in these patients, there was no significant difference in short-term mortality or length of hospital stay between those with AF and those without.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atrial fibrillation after surgery for esophageal carcinoma: clinical and prognostic significance. Ma, JY., Wang, Y., Zhao, YF., et al.[2019]

In a study of 220 matched patients who underwent esophagectomy, prophylactic intravenous amiodarone significantly reduced the incidence of atrial fibrillation (AF) requiring treatment, with 15.5% in the amiodarone group compared to 29.1% in the control group.

While amiodarone effectively lowered AF rates, it was associated with higher risks of hypotension, bradycardia, and prolonged QT intervals, indicating potential safety concerns despite its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone for prevention of atrial fibrillation following esophagectomy. Tisdale, JE., Jaynes, HA., Watson, MR., et al.[2020]

In a study of 27 patients, those who underwent esophagectomy had significantly lower serum amiodarone concentrations after nasogastric administration compared to patients who had pulmonary resection, indicating poor absorption of the drug in the esophagectomy group.

On postoperative days 2 and 4, a notable percentage of patients in the esophagectomy group had undetectable levels of amiodarone, suggesting that nasogastric administration may not be effective for preventing or treating atrial fibrillation after esophagectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of serum amiodarone concentrations when administered via a nasogastric tube into the stomach conduit after transthoracic esophagectomy. Tisdale, JE., Wroblewski, HA., Hammoud, ZT., et al.[2013]

In a study of 207 esophageal cancer patients who underwent transthoracic esophagectomy, postoperative atrial fibrillation (AF) occurred in 9.2% of patients, with effective antiarrhythmic treatment in 63.2% of cases.

Postoperative AF was significantly linked to the use of an ileo-colon for reconstruction and the presence of tachycardia (heart rate >100 bpm) on the first postoperative day, highlighting the importance of identifying high-risk patients for targeted prophylactic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atrial fibrillation after esophageal cancer surgery: an analysis of 207 consecutive patients. Ojima, T., Iwahashi, M., Nakamori, M., et al.[2021]

In a study of 60 patients with arrhythmias after esophageal and lung cancer surgery, amiodarone was found to be significantly more effective than cedilan, with a higher treatment success rate and faster onset of action.

Patients treated with amiodarone also experienced better cardiac function, lower ventricular rates, and fewer adverse reactions compared to those treated with cedilan, indicating it may be a safer and more effective option for managing postoperative arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of Amiodarone and Cedilan in the Treatment of Patients with Arrhythmia after Esophageal and Lung Cancer. Ge, H.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy. [2015]

2. Germany pubmed.ncbi.nlm.nih.gov

Amiodarone is a cost-neutral way of preventing atrial fibrillation after surgery for lung cancer. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Atrial fibrillation after surgery for esophageal carcinoma: clinical and prognostic significance. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Amiodarone for prevention of atrial fibrillation following esophagectomy. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Prospective evaluation of serum amiodarone concentrations when administered via a nasogastric tube into the stomach conduit after transthoracic esophagectomy. [2013]

6. Japan pubmed.ncbi.nlm.nih.gov

Atrial fibrillation after esophageal cancer surgery: an analysis of 207 consecutive patients. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Application of Amiodarone and Cedilan in the Treatment of Patients with Arrhythmia after Esophageal and Lung Cancer. [2023]