Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT03752931 |
| Other study ID # |
MAMICELDIL |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
December 2018 |
| Est. completion date |
December 2020 |
Study information
| Verified date |
November 2018 |
| Source |
Abderrahmane Mami Hospital |
| Contact |
MARZOUK Mahmoud, MD |
| Phone |
0021620874718 |
| Email |
mahmoudmarzouk[@]hotmail.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Cardiac arrythmias are the most common cardiac complications after thoracic surgery. They are
made primarily of postoperative atrial fibrillation (POAF).
They are associated with an increased risk of stroke, increased length of hospital stay and
cost of care, and increased long-term mortality.
Randomized , single-blind prospective study in the anesthesia and intensive care department
of Abderrahmen Mami hospital Ariana Tunisia comparing the efficacy of Diltiazem versus
Celiprolol in the prevention of postoperative cardiac arrythmias in patients proposed for
pneumonectomy and bilobectomy.
Description:
Cardiac arrythmias are the most common cardiac complications after thoracic surgery. They are
made primarily of postoperative atrial fibrillation (POAF).
They are associated with an increased risk of stroke, increased length of hospital stay and
cost of care, and increased long-term mortality.
According to the American Association of Thoracic Surgery (AATS), interventions at high risk
for FAPO (> 15%) are: anterior mediastinal mass resection, thoracoscopic lobectomy,
thoracotomy lobectomy, pneumonectomy, pleurectomy, tracheal resection, emphysema bubble,
bronchopleural fistula repair, lung transplantation and oesophagectomy. And it has been shown
that the occurrence of postoperative atrial fibrillation is correlated with the extent of
resection in case of lung resection surgery such as lobectomy or pneumonectomy.
Based on their multifactorial etiology, different pharmacological classes have been used for
the prevention of POAF with varying degrees of success such as Amiodarone, Digoxin, Flecaine,
Magnesium Sulfate, Beta Blockers, Calcium Inhibitors and Statins.
Recommendations were made for the prevention of POAF by the Society of Thoracic Surgeons
(STS) in 2011 and the AATS in 2014 and concluded that Diltiazem is recommended for prevention
and it is a Grade IIA for recommendations of 2011 and a grade IIB for the 2014
recommendations. Beta-blockers (BB) are recommended and it is a grade IIB for the 2011
recommendations. In addition, amiodarone is not recommended in case of pneumonectomy because
of of its pulmonary toxicity for the 2011 recommendations and is ranked grade IIA for the
2014 recommendations.
A meta-analysis published in Chest in 2017 involving 22 studies and 2891 patients showed that
the pharmacological prevention of postoperative rhythm disorders after thoracic surgery
decreases their incidence but does not reduce mortality in the short term. Several drugs have
been studied. Betablockers have the probability of being the most effective agent. Calcium
inhibitors are less effective.
In view of these conflicting results and in the absence of a large randomized controlled
trial comparing two pharmacologic agents for the prevention of POAF, a certain degree of
uncertainty persists regarding the superiority of one agent over another. especially in case
of pulmonary resection surgery. Most studies compare drugs versus placebo. Among these drugs
Diltiazem and BB are among the most effective and safe.
Randomized , single-blind prospective study in the anesthesia and chest surgery departments
of Abderrahmen Mami hospital Ariana Tunisia.
The objective is to compare the efficacy of Celiprolol -Class II of cardioselective
anti-arrhythmic B1 with B2 agonist activity with intrinsic sympathomimetic activity- versus
Diltiazem -Class IV antiarrhythmic calcium antagonist with direct cardiac effects- in the
prevention of cardiac arrhythmias after thoracic surgery such as bilobectomy and
pneumonectomy.
Have been included:
- Age ≥ 18 years
- Sinus rhythm preoperatively.
- Surgery at high risk of atrial arrhythmia occurring postoperatively:
Bi-lobectomy Pneumonectomy
Have not been included:
- history of cardiac arrhythmia.
- A prior history of atrio-ventricular block with non-paired degrees II or III.
- Patients on calcium channel blockers or beta-blockers as background therapy.
- Hypersensitivity to Diltiazem and / or Celiprolol and / or any of the excipients.
- Renal insufficiency with creatinine clearance <40 ml / min.
- wolf parkinson white syndrome.
- Myasthenia gravis.
- Chronic Obstructive Pulmonary Disease: GOLD III or IV.
Have been excluded :
• Signs of myocardial ischemia per or post operative.
• Persistent postoperative hypotension requiring the use of catecholamines.
- Persistent bradycardia.
- Decompensated cardiac insufficiency.
- Acute bowel obstruction.
* The main criterion of judgment:
- Incidence of early postoperative atrial fibrillation.
* Secondary criteria for judgment:
- The incidence of late arrhythmia (> 14 days) during or after hospitalization during the
30 postoperative days.
- The incidence of other rhythm disorders.
- The duration of the arrhythmia in case of occurrence.
- Length of stay in intensive care unit and hospital.
- 30-day mortality.
- Other complications during 14 days postoperative:
Pulmonary: Atelectasis, pneumonitis, ARDS, Cardiovascular: heart failure, heart attack,
pulmonary embolism. Neurological: stroke Acute renal failure. • Product Tolerance: Digestive
Disorders, Dizziness, Bradycardia, Hypotension, Bronchospasm, Hypoglycemia or Hyperglycemia.
* Perioperative management:
- Preoperatively:
All patients are assessed at the pre-anesthetic consultation. All patients are informed about
postoperative treatment to reduce the incidence of arrhythmias.
A consent form is signed for this purpose.
- Inoperative:
- General anaesthesia:
Induction: Fentanyl, Propofol, Cisatracurium Maintenance: Propofol to push electric syringe,
fentanyl and cisatracurium.
- Perioperative fluid restriction <25ml / kg / 24h with isotonic saline as much as
possible.
- The extent of pericardial resection and mediastinal lymph node dissection are mentioned.
- Bleeding estimated peroperatively, the need for catecholamines, labile blood products
and intraoperative incidents are noted.
- Postoperative analgesia combines Paracetamol 1g per 6 hours with thoracic epidural
analgesia or multimodal analgesia with morphine titration as needed.
Postoperatively:
- All patients are admitted to intensive care.
- Close monitoring of hemodynamic, respiratory and neurological parameters.
- Patients are randomized into 2 groups:
Group 1: receiving 1 tablet per day of celiprolol 200 mg in the morning from the first day
after surgery.
Group 2: receiving 1 capsule per day of diltiazem 200 mg in the morning from the first
postoperative day.
The target heart rate is between 70 and 80 bpm by titrating the antiarrhythmic agent.
The treatment will be continued for 14 days.
- electrocardiogram at 6 hours postoperative or if clinical suspicion of arrhythmia or
modification to the scope then twice a day.
- Postoperative blood count.
- Magnesemia, phosphoremia, calcemia, and blood ionogram at the first postoperative day
and correction if abnormalities.
- X-ray of the postoperative chest and 1 time per day especially for the research of
deviation of the mediastinum in case of pneumonectomy.
The occurrence of an arrhythmia will be treated according to the following algorithm:
- Look for probable cause of bleeding, pulmonary embolism, pneumothorax, pericardial
effusion, mediastinal deviation, hypoxia, myocardial ischemia or sepsis.
- Optimize the volemia.
- Correct metabolic disorders.
- Optimize analgesia.
- If hemodynamically unstable:
Of duration <48 h: external electric shock and advice cardiology. Duration> 48 h: consider
anticoagulation, external electrical shock and cardiology.
-It is hemodynamically stable
Duration <48h:
Consider anticoagulation if CHA2DS2 score VASc> 1, amiodarone IV then per os and notice
cardiology.
Duration> 48h: consider anticoagulation, IV amiodarone then per os and opinion cardiology.
• All patients are referred to outpatient cardiology consultations with a rhythmic holter
upon discharge.
The occurrence of another postoperative complication will be noted by specifying the date of
occurrence in relation to the arrhythmia:
- Pulmonary: Atelectasis, pneumonitis, ARDS, need for prolonged mechanical ventilation.
- Cardiovascular: heart failure, myocardial infarction, pulmonary embolism.
- Neurological: Stroke
- Acute renal failure.
