Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000297729
Ethics application status
Approved
Date submitted
25/08/2021
Date registered
16/02/2022
Date last updated
16/02/2022
Date data sharing statement initially provided
16/02/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Obesity effect on the characteristics of the blood-thinning drug rivaroxaban
Scientific title
The Effect of Obesity on the Pharmacokinetic and Pharmacodynamic Disposition of Rivaroxaban in Patients with Venous Thromboembolism (VTE) or Non-valvular Atrial Fibrillation (AF)
Secondary ID [1] 305009 0
MRC-01-18-460
Universal Trial Number (UTN)
Trial acronym
EPHORIA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
venous thromboembolism 323359 0
atrial fibrillation 323360 0
obesity 323361 0
Condition category
Condition code
Cardiovascular 320931 320931 0 0
Diseases of the vasculature and circulation including the lymphatic system
Metabolic and Endocrine 320932 320932 0 0
Other metabolic disorders
Blood 321814 321814 0 0
Clotting disorders
Cardiovascular 321815 321815 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Rivaroxaban is the exposure drug.
If the primary physician decided to start the patient on rivaroxaban, they will be screened for enrollment in this study.
It will be prescribed and administered to morbidly obese patients (body weight >120 kg or BMI of 40 kg/m2 or more, and patients with BMI 30 to <35 kg/m2 ) who present with venous thromboembolisms (including deep vein thrombosis or pulmonary embolisms) or atrial fibrillation if no contraindications exist.
We will draw blood samples at different time-points starting pre-dose and up to 96 hours after the first dose to measure the drug concentration at the blood and draw the area under the curve (AUC) graph for morbidly obese vs. the control group. In addition to comparing drug concentration among groups, we will also explore the difference in the pharmacodynamics of the drug as well as any genetic polymorphisms that might explain any differences.
Rivaroxaban dose is 15 mg oral tablet twice daily for 21 days then 20 mg oral tablet once daily thereafter for the treatment of acute venous thromboembolism. However, patients will be recruited to this study for up to 96 hours only. The total duration of treatment will depend on the medical condition and patient comorbidities and will be decided by the primary physicians.
Dose for non-valvular atrial fibrillation is 20 mg tablet orally once daily.
Intervention code [1] 321534 0
Not applicable
Comparator / control treatment
The control group includes patients with BMI 18.5 to <25 kg/m2
The control group will receive the same intervention as the intervention group.
Control group
Active

Outcomes
Primary outcome [1] 328714 0
Pharmacokinetic parameters (Cmax, AUC, t1/2) of rivaroxaban assessed using blood samples withdrawn starting pre-dose and up to 12 hours post dose.
Timepoint [1] 328714 0
Predose, and at 1, 2, 4, 8, and 12 hours post-dose.
Secondary outcome [1] 400099 0
The pharmacodynamic parameters (factor Xa activity) of rivaroxaban assessed using blood samples at 96 hours post dose.
Timepoint [1] 400099 0
At 96 hours post-dose.

Eligibility
Key inclusion criteria
• Adults with age greater than or equal to 18 years
• Diagnosis of DVT, PE, or non-valvular atrial fibrillation
• Admission to medical ward or emergency department in Hamad General Hospital
• Eligibility for rivaroxaban treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Abnormal kidney function (CrCl of less than 30 ml/min)
• Severe liver disease
• Valvular heart disease
• Hemodynamic instability or current admission to intensive care units
• Active bleeding or high bleeding risk
• Patients with extremely low weight (less than 50 kg)
• Antiphospholipid antibody syndrome
• Any other contraindications to rivaroxaban

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Sample Size Calculation:
Using independent-sample T-Test, we calculated that we would need a sample size of 21 in each group to reliably (with probability greater than 0.8) detect an effect size of 0.9 assuming a two-sided criterion
for detection that allows for a maximum Type I error rate of 0.05. To account for 30% dropouts, 18 patients will be added to the total sample size for the three groups, 63 + 18 = 81 (i.e. 27 patients per group).

Statistical Methods:
Baseline and follow up characteristics will be presented as means (± SD), or median (IQR) as appropriate. Within and between group differences will be determined by Wilcoxon Rank test/Mann Whitney test or ANOVA respectively. Corrolation coefficient between study variables will be determined by Pearson or Spearman’s Corrolation coefficient depending on distribution of the data. Significant variables from bivariate analysis will be entered into regression models to ascertain predictors of rivaroxaban response.
All statistics will be carried out using SPSS® Version 22.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
17/11/2021
Date of last participant enrolment
Anticipated
31/12/2022
Actual
Date of last data collection
Anticipated
5/01/2023
Actual
Sample size
Target
81
Accrual to date
2
Final
Recruitment outside Australia
Country [1] 24058 0
Qatar
State/province [1] 24058 0
Doha

Funding & Sponsors
Funding source category [1] 309399 0
Government body
Name [1] 309399 0
Medical Research Center, Hamad Medical Corporation
Country [1] 309399 0
Qatar
Primary sponsor type
Government body
Name
Medical Research Center, Hamad Medical Corporation
Address
P.O. Box 3050
Hamad Medical Corporation
Doha, Qatar
Country
Qatar
Secondary sponsor category [1] 310368 0
University
Name [1] 310368 0
Qatar University
Address [1] 310368 0
P.O. Box 2713
College of Pharmacy, Qatar University
Doha, Qatar
Country [1] 310368 0
Qatar

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309205 0
Hamad Medical Corporation Institutional Review Board
Ethics committee address [1] 309205 0
HMC-IRB Office
Hamad Medical City
Al Khalej Street, Doha, Qatar
P.O. Box 3050
Ethics committee country [1] 309205 0
Qatar
Date submitted for ethics approval [1] 309205 0
Approval date [1] 309205 0
04/05/2020
Ethics approval number [1] 309205 0
IRB-A-HMC-2019- 0014

Summary
Brief summary
This research is being conducted to investigate the effect of body weight on the characteristics (mainly the plasma drug concentration) of a blood-thinning drug known as rivaroxaban. This drug is used for the treatment of blood clots, and for the prevention of stroke in a certain heart-related disease known as Atrial Fibrillation. Participants in this research will provide blood samples during their enrollment period, and these samples will be used to quantify drug concentration in patients with body weight greater than 120 kg or BMI of greater than or equal to 40 kg/m2 , in order to compare that to non-morbidly obese patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113334 0
Dr Ibtihal Mahmoud Hassan Abdallah
Address 113334 0
Hamad General Hospital, Hamad Medical Corporation
P.O. Box 3050, Doha
Country 113334 0
Qatar
Phone 113334 0
+97444392186
Fax 113334 0
Email 113334 0
[email protected]
Contact person for public queries
Name 113335 0
Dr Ibtihal Mahmoud Hassan Abdallah
Address 113335 0
Hamad General Hospital, Hamad Medical Corporation
P.O. Box 3050, Doha
Country 113335 0
Qatar
Phone 113335 0
+97444392186
Fax 113335 0
Email 113335 0
[email protected]
Contact person for scientific queries
Name 113336 0
Dr Ibtihal Mahmoud Hassan Abdallah
Address 113336 0
Hamad General Hospital, Hamad Medical Corporation
P.O. Box 3050, Doha
Country 113336 0
Qatar
Phone 113336 0
+97444392186
Fax 113336 0
Email 113336 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie published results only
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following main results publication
Available to whom?
On case-by-case basis at the discretion of Primary Sponsor.
Available for what types of analyses?
IPD meta-analyses
How or where can data be obtained?
Access subject to approvals by Principal Investigator ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.