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Gender Influence on Torsadogenic Actions of Droperidol.
Postoperative nausea and vomiting (PONV) is a quite common complication affecting patients undergoing general anesthesia. There are a few pharmacological agents of well known effectiveness in reducing the risk of PONV. One of them is droperidol, which is a butyrophenone derivant. It has been widely used for the prevention and treatment of PONV due to its high effectiveness and low cost. Though, droperidol has a relevant side effect, that is a repolarization prolongation. This can lead to life-threatening cardiac arrhythmias: polymorphic ventricular tachycardia (torsades de pointes, TdP) that can degenerate into ventricular fibrillation and cardiac arrest. This was a reason why in 2001 the FDA issued a "black box" warning on droperidol. Ever since papers focused on this problem have described the influence of small doses of droperidol on TdP genesis as weak. This could be explained by the fact, that QT/QTc (corrected QT) interval prolongation, which represents prolonged cardiac repolarization on ECG, is not the sole determinant of a drug's potential to cause arrhythmia. Another electrocardiographical marker of torsadogenic action is increased transmural dispersion of repolarization (TDR). TDR represents differences in the repolarization between myocardial "layers" (like epicardium, endocardium, myocardium cells). It is believed that the induction of QT/QTc lengthening must coexist with TDR increase at the same time to promote torsadogenic changes.
It has been known, on the basis of research, that females have been more potent to torsadogenic actions of pharmacological agents than males. That could be related to estrogen influence on ECG parameters, which had been proven on animal model. It hasn't been investigated, whether gender is an important factor when considering droperidol's torsadogenic potential.
The aim of this study is to answer a hypothesis, that women are more potent to torsadogenic actions of droperidol in comparison with men.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Arrhythmia, Droperidol | Drug: Droperidol Injectable Solution | Not Applicable |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 70 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Supportive Care |
| Official Title: | Gender Influence on Torsadogenic Actions of Droperidol Used as Postoperative Nausea and Vomiting Prophylaxis. |
| Actual Study Start Date : | April 23, 2019 |
| Estimated Primary Completion Date : | December 2020 |
| Estimated Study Completion Date : | December 2020 |
| Arm | Intervention/treatment |
|---|---|
|
Droperidol group
Droperidol (Xomolix, Kyowa Kirin) 1.25 mg i.v. bolus
|
Drug: Droperidol Injectable Solution
An electrocardiogram analysis in: 5,10,15,20 minutes after injection of 1.25 mg of droperidol used as PONV prophylaxis.
Other Name: electrocardiogram analysis
|
- QT and corrected QT interval time [ Time Frame: Change from baseline QT and corrected QT interval time at 5,10,15 and 20 minutes after administration of 1.25 mg droperidol ]measured in milliseconds
- Time interval between T wave peak and T wave end [ Time Frame: Change from baseline T peak - T end time at 5,10,15 and 20 minutes after administration of 1.25 mg droperidol. ]measured in milliseconds
| Ages Eligible for Study: | 18 Years to 45 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- age between 18 and 45 years old
- ASA (American Society of Anaesthesiologists) physical status 1 and 2
Exclusion Criteria:
- lack of informed consent
- ASA (American Society of Anaesthesiologists) physical status 3 and more
- admittance of repolarisation affecting drugs like: antiarrhythmics (Williams group I-IV), psychotropics, macrolides, antireflux drugs
- ischaemic heart disease
- cardiac failure NYHA (Hew York Heart Association) 1 and more
- congenital or acquired heart defects
- arrhythmias in anamnesis
- hormonal contraception,
- postmenopausal
- neoplasms
| Contact: Karol Broniecki, MD | +48 58 726 02 87 | k.broniecki@hotmail.com |
| Poland | |
| Medical University of Gdansk | Recruiting |
| Gdansk, Poland, 80211 | |
| Contact: Radoslaw Owczuk, Prof. (+48) 58 349 32 80 radoslaw.owczuk@gumed.edu.pl | |
| Contact: Karol Broniecki, MD (+48) 58 726 02 87 k.broniecki@hotmail.com | |
| Principal Investigator: | Radoslaw Owczuk, Professor | Medical University of Gdansk |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | January 30, 2019 | ||||
| First Posted Date ICMJE | May 9, 2019 | ||||
| Last Update Posted Date | September 10, 2020 | ||||
| Actual Study Start Date ICMJE | April 23, 2019 | ||||
| Estimated Primary Completion Date | December 2020 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
|
||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE | Not Provided | ||||
| Original Secondary Outcome Measures ICMJE | Not Provided | ||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Gender Influence on Torsadogenic Actions of Droperidol. | ||||
| Official Title ICMJE | Gender Influence on Torsadogenic Actions of Droperidol Used as Postoperative Nausea and Vomiting Prophylaxis. | ||||
| Brief Summary |
Postoperative nausea and vomiting (PONV) is a quite common complication affecting patients undergoing general anesthesia. There are a few pharmacological agents of well known effectiveness in reducing the risk of PONV. One of them is droperidol, which is a butyrophenone derivant. It has been widely used for the prevention and treatment of PONV due to its high effectiveness and low cost. Though, droperidol has a relevant side effect, that is a repolarization prolongation. This can lead to life-threatening cardiac arrhythmias: polymorphic ventricular tachycardia (torsades de pointes, TdP) that can degenerate into ventricular fibrillation and cardiac arrest. This was a reason why in 2001 the FDA issued a "black box" warning on droperidol. Ever since papers focused on this problem have described the influence of small doses of droperidol on TdP genesis as weak. This could be explained by the fact, that QT/QTc (corrected QT) interval prolongation, which represents prolonged cardiac repolarization on ECG, is not the sole determinant of a drug's potential to cause arrhythmia. Another electrocardiographical marker of torsadogenic action is increased transmural dispersion of repolarization (TDR). TDR represents differences in the repolarization between myocardial "layers" (like epicardium, endocardium, myocardium cells). It is believed that the induction of QT/QTc lengthening must coexist with TDR increase at the same time to promote torsadogenic changes. It has been known, on the basis of research, that females have been more potent to torsadogenic actions of pharmacological agents than males. That could be related to estrogen influence on ECG parameters, which had been proven on animal model. It hasn't been investigated, whether gender is an important factor when considering droperidol's torsadogenic potential. The aim of this study is to answer a hypothesis, that women are more potent to torsadogenic actions of droperidol in comparison with men. |
||||
| Detailed Description | Not Provided | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Not Applicable | ||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Supportive Care |
||||
| Condition ICMJE | Arrhythmia, Droperidol | ||||
| Intervention ICMJE | Drug: Droperidol Injectable Solution
An electrocardiogram analysis in: 5,10,15,20 minutes after injection of 1.25 mg of droperidol used as PONV prophylaxis.
Other Name: electrocardiogram analysis
|
||||
| Study Arms ICMJE | Droperidol group
Droperidol (Xomolix, Kyowa Kirin) 1.25 mg i.v. bolus
Intervention: Drug: Droperidol Injectable Solution
|
||||
| Publications * | Not Provided | ||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||
| Recruitment Information | |||||
| Recruitment Status ICMJE | Recruiting | ||||
| Estimated Enrollment ICMJE |
70 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Estimated Study Completion Date ICMJE | December 2020 | ||||
| Estimated Primary Completion Date | December 2020 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||
| Sex/Gender ICMJE |
|
||||
| Ages ICMJE | 18 Years to 45 Years (Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE |
|
||||
| Listed Location Countries ICMJE | Poland | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03944681 | ||||
| Other Study ID Numbers ICMJE | KB01 | ||||
| Has Data Monitoring Committee | No | ||||
| U.S. FDA-regulated Product |
|
||||
| IPD Sharing Statement ICMJE |
|
||||
| Responsible Party | Radoslaw Owczuk, Medical University of Gdansk | ||||
| Study Sponsor ICMJE | Medical University of Gdansk | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
|
||||
| PRS Account | Medical University of Gdansk | ||||
| Verification Date | September 2020 | ||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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