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Study of Ondansetron in the Prevention of Sleep Syncope: The Nineth Prevention of Syncope Trial (POST9) (POST9)

Primary Purpose

Sleep Syncope

Status
Not yet recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
ondansetron 8 mg
Matching placebo
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sleep Syncope focused on measuring Ondansetron

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Syncope according to the American College of Cardiology Guidelines 2017 ≥1 Sleep Syncope in the year preceding enrolment ≥-2 points on the Calgary Syncope Symptom Score for Structurally Normal Hearts Age ≥ 18 years with informed consent. Exclusion Criteria: An inability to give informed consent pregnancy, unwilling or unable to use adequate birth control while on study drug QT interval exceeding 500 ms in the absence of correctable factors.

Sites / Locations

  • University of Calgary

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Ondansetron

Placebo

Arm Description

ondansetron 8 mg prn sublingually when awakening with nausea. as per the FDA label for ondansetron.

Matching placebo will be identical in appearance to the active treatment pill.

Outcomes

Primary Outcome Measures

nausea event causing the patient to awake and prevented from progressing to syncope
One nausea event causing the patient to awake and prevented from progressing to syncope

Secondary Outcome Measures

In a substudy we will test whether the predominant disturbed physiology is bradycardia, decreased venous return, or decreased systemic vascular resistance
This will be assessed using a unique, small wearable blood pressure sensor that can be donned rapidly on the ear.
Hospital Anxiety and Depression Scale (HADS)
The total score is out of 42, (21 per subscale). Scores are derived by summing responses for each of the two subscales or for the scale as a whole Higher scores indicate greater levels of anxiety or depression. The total HADS score may be regarded as a global measure of psychological distress
Generalized Anxiety Disorder score
The GAD-7 is useful in primary care and mental health settings as a screening tool and symptom severity measure for the four most common anxiety disorders (Generalized Anxiety Disorder, Panic Disorder, Social Phobia and PostTraumatic Stress Disorder). It is 70-90% sensitive and 80-90% specific across disorders / cutoffs (see Evidence section for more). Higher GAD-7 scores correlate with disability and functional impairment (in measures such as work productivity and health care utilization)
EQ-5D-3L
The EQ-5D-3L classification system consists of five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, each with three levels: no problems "1", moderate problems "2", and severe problems "3". Each health state is described as a vector of these five dimensions. With 3 levels for each dimension, the EQ-5D-3L describes 243 distinct health states, with 11111 being the best health state (full health), and 33333 the worst health state. In addition to the classification system, each of the instruments also includes a visual analogue scale (EQ VAS). The EQ VAS records the respondent's self-rated health on a visual analogue scale from 0 to 100, whereby 0 indicates 'the worst health you can imagine', and 100 'the best health you can imagine'. This information can be used as a quantitative measure of health as judged by the individual respondents.
Impact of Syncope on Quality of Life
The ISQL is a brief valid measure of the impact of syncope on quality of life. It measures impairment, fear, depression, and physical limitations, and correlates with recent syncope frequency.
The Short-Form (SF-36) Health Survey
The SF-36 is a multi-purpose survey designed to capture adult patients' perceptions of their own health and well-being.

Full Information

First Posted
December 12, 2022
Last Updated
April 5, 2023
Sponsor
University of Calgary
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1. Study Identification

Unique Protocol Identification Number
NCT05657925
Brief Title
Study of Ondansetron in the Prevention of Sleep Syncope: The Nineth Prevention of Syncope Trial (POST9)
Acronym
POST9
Official Title
Randomized, Prospective, Placebo-Controlled, Crossover Study of Ondansetron in the Prevention of Sleep Syncope: The Nineth Prevention of Syncope Trial (POST9)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2023 (Anticipated)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Calgary

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
At least 5% of patients with vasovagal syncope also have Sleep Syncope. Patients awake from sleep with profound malaise and gastrointestinal vagal symptoms. About 75% have severe nausea and about 40% have lower abdominal cramps. Some faint while supine, but most find their symptoms so severe that they rise quickly and hurry to the bathroom. Sometime either on the way to the toilet, near it, or shortly afterwards they faint. The nausea is followed by vomiting, and the cramps by watery diarrhea. After relief the patients remain presyncopal, diaphoretic, and tired. Almost all patients also have clinical vasovagal syncope during daytime hours. The cause of this is unknown. Orthostatic stress cannot be a factor in triggering the event, and in isolated case reports it occurs during non-REM sleep. There is no classic provocative situation of pain, the sight of trauma, or the presence of medical settings. These suggest the importance of central processes and the reduced likelihood that strategies that target maintaining preload (such as with midodrine and fludrocortisone) would be helpful. As well, midodrine is avoided during the night. Recently the investigators reasoned that if the investigators could rapidly suppress the nausea patients could remain supine, wait out the nausea, and not faint with orthostatic stress. Ondansetron is a potent anti-nausea medication that has rapidly dissolving preparations. Nine patients were instructed to keep one at the bedside, insert it upon waking up with nausea, remain in bed, and raise their legs (if possible). There was partial success with ondansetron 4 mg and complete success with ondansetron 8 mg. This remarkable but anecdotal observation requires formal testing. Research Objectives: the investigators will test the hypothesis that ondansetron 8 mg prn sublingually on awakening with moderate to severe nausea prevents loss of consciousness in patients with prior Sleep Syncope who awaken with malaise and nausea. Study Design & Methodology: The main study will be a placebo-controlled, double-blind, randomized, crossover clinical trial. The primary outcome will be the progression of awakening with nausea to syncope. Thirty patients with Sleep Syncope will be randomized 1:1 to receive packages of either ondansetron 8 mg sublingual tablets or matching placebo. They will each receive 3 boxes of 10 tabs, with refills available if needed. Each crossover period will last 6 months. In a substudy the investigators will test whether the predominant disturbed physiology is bradycardia, decreased venous return, or decreased systemic vascular resistance. This will be assessed using a unique, small, wearable blood pressure sensor that can be rapidly donned on the ear. It records heart rate and beat-to-beat waveforms, which permit estimating stroke volume, systemic vascular resistance, and cardiac output. the investigators will record these variables in all patients continuously from when the device is put on until 30 minutes afterwards. the investigators hypothesize that unlike during syncope provoked by head-up tilt testing, here there will be no decrease in preload until patients arise, and that the main physiologic disturbance during syncope is hypotension due to decreased preload superimposed on heart rate collapse. Anticipated Outcomes: If successful, this research would be i) the first to report a well-tolerated and highly effective treatment for most sleep syncope, and ii) the first to report the physiology of brain-initiated vasovagal syncope in the community outside a laboratory environment.
Detailed Description
Trial interventions: Randomization will be to ondansetron 8 mg sublingual tablets or matching placebo tablets kept at the bedside, to be used upon awakening with premonitory nausea. This is a commonly used dose for rapid treatment of nausea. Randomization: Patients will be randomized into two treatment groups will be carried out centrally with a randomization scheme using a computerized algorithm. Medication containers will be filled and labelled with the randomization code number centrally. The investigators will complete a screening log of eligible but nonrandomized patients that will contain demographic data and the reason for non-randomization. Followup: Study nurse coordinators will see the patients in clinic at baseline, 3 months, 6 months, 9 months, and 12 months. The 6-month visit will be the visit during which the patients will be crossed over from one arm to the other. The total study duration will be 52 weeks for each participant. Patients will be asked to notify the study nurse if they experience a premonitory nausea awakening either with or without an ensuing syncope. Pill counts will be conducted to confirm the number of events.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Syncope
Keywords
Ondansetron

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ondansetron
Arm Type
Active Comparator
Arm Description
ondansetron 8 mg prn sublingually when awakening with nausea. as per the FDA label for ondansetron.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo will be identical in appearance to the active treatment pill.
Intervention Type
Drug
Intervention Name(s)
ondansetron 8 mg
Intervention Description
Ondansetron 8 mg prn sublingually when awakening with nausea. as per the FDA label for ondansetron.
Intervention Type
Drug
Intervention Name(s)
Matching placebo
Intervention Description
Matching placebo will be identical in appearance to the active treatment pill
Primary Outcome Measure Information:
Title
nausea event causing the patient to awake and prevented from progressing to syncope
Description
One nausea event causing the patient to awake and prevented from progressing to syncope
Time Frame
Within 12 months period of the study
Secondary Outcome Measure Information:
Title
In a substudy we will test whether the predominant disturbed physiology is bradycardia, decreased venous return, or decreased systemic vascular resistance
Description
This will be assessed using a unique, small wearable blood pressure sensor that can be donned rapidly on the ear.
Time Frame
Within 12 months period of the study
Title
Hospital Anxiety and Depression Scale (HADS)
Description
The total score is out of 42, (21 per subscale). Scores are derived by summing responses for each of the two subscales or for the scale as a whole Higher scores indicate greater levels of anxiety or depression. The total HADS score may be regarded as a global measure of psychological distress
Time Frame
every 6 months of the study up to 12 months
Title
Generalized Anxiety Disorder score
Description
The GAD-7 is useful in primary care and mental health settings as a screening tool and symptom severity measure for the four most common anxiety disorders (Generalized Anxiety Disorder, Panic Disorder, Social Phobia and PostTraumatic Stress Disorder). It is 70-90% sensitive and 80-90% specific across disorders / cutoffs (see Evidence section for more). Higher GAD-7 scores correlate with disability and functional impairment (in measures such as work productivity and health care utilization)
Time Frame
every 6 months of the study up to 12 months
Title
EQ-5D-3L
Description
The EQ-5D-3L classification system consists of five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, each with three levels: no problems "1", moderate problems "2", and severe problems "3". Each health state is described as a vector of these five dimensions. With 3 levels for each dimension, the EQ-5D-3L describes 243 distinct health states, with 11111 being the best health state (full health), and 33333 the worst health state. In addition to the classification system, each of the instruments also includes a visual analogue scale (EQ VAS). The EQ VAS records the respondent's self-rated health on a visual analogue scale from 0 to 100, whereby 0 indicates 'the worst health you can imagine', and 100 'the best health you can imagine'. This information can be used as a quantitative measure of health as judged by the individual respondents.
Time Frame
every 6 months of the study up to 12 months
Title
Impact of Syncope on Quality of Life
Description
The ISQL is a brief valid measure of the impact of syncope on quality of life. It measures impairment, fear, depression, and physical limitations, and correlates with recent syncope frequency.
Time Frame
every 6 months of the study up to 12 months
Title
The Short-Form (SF-36) Health Survey
Description
The SF-36 is a multi-purpose survey designed to capture adult patients' perceptions of their own health and well-being.
Time Frame
every 6 months of the study up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Syncope according to the American College of Cardiology Guidelines 2017 ≥1 Sleep Syncope in the year preceding enrolment ≥-2 points on the Calgary Syncope Symptom Score for Structurally Normal Hearts Age ≥ 18 years with informed consent. Exclusion Criteria: An inability to give informed consent pregnancy, unwilling or unable to use adequate birth control while on study drug QT interval exceeding 500 ms in the absence of correctable factors.
Facility Information:
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 1N4
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Sheldon
Phone
4032108510
Email
sheldon@ucalgary.ca
First Name & Middle Initial & Last Name & Degree
Rasha Hamzeh
Phone
4032208897
Email
rasha.hamzeh1@ucalgary.ca

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Ondansetron in the Prevention of Sleep Syncope: The Nineth Prevention of Syncope Trial (POST9)

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