Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000730404
Ethics application status
Approved
Date submitted
20/06/2025
Date registered
8/07/2025
Date last updated
8/07/2025
Date data sharing statement initially provided
8/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Coagulation assessment of sublingual oestrogen (CASE) trial
comparison of clotting profile and risk in transgender females on oral vs sublingual estrogen for gender affirming hormonal therapy
Scientific title
Coagulation assessment of sublingual oestrogen (CASE) trial
comparison of coagulation risk profile in transgender females on oral vs sublingual estrogen for gender affirming hormonal therapy
Secondary ID [1] 314707 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
CASE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Venous Thromboembolism (VTE) 337896 0
Gender affirming estrogen therapy 337895 0
Condition category
Condition code
Blood 334230 334230 0 0
Clotting disorders
Metabolic and Endocrine 334231 334231 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
comparison of coagulation profile of oral and sublingual routes of administration of oestradiol for gender affirming hormonal therapy in transgender females.

intervention: sublingual administration of oestradiol for gender affirming hormonal therapy. oestradiol (2 mg, Zumenon®, once daily orally for three months)
-drug adherence will be monitored via serum oestradiol levels on clinical review

patients will crossover from control to intervention arm or intervention to control arm based on a randomisation schedule
there is no washout period between crossover, patient will be on given gender affirming therapy for 3 months to assess steady state VTE risk
Intervention code [1] 331315 0
Treatment: Drugs
Comparator / control treatment
control: oral administration of oestradiol for gender affirming hormonal therapy (4 mg, Progynova®, once daily for three months)
Control group
Active

Outcomes
Primary outcome [1] 341889 0
Coagulation profile: composite outcome (global coagulation assay) that will be measured via GCA/CAT + Overall haemostatic potential assay
Timepoint [1] 341889 0
baseline, 3 months after control arm and 3 months after intervention arm.
Secondary outcome [1] 448898 0
Pharmacokinetic comparison of serum oestradiol levels in oral vs sublingual oestrodiol
Timepoint [1] 448898 0
0 hours (trough) , 1 hour, 2 hour, 3 hour, 4hour, 6 hours, 8 hours post oral or sublingual oestradiol dose

Eligibility
Key inclusion criteria
1. Age 18 to 40 years old
2. currently on or commencing prescribed oestrogen as feminising gender affirming hormone therapy
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who are taking moderate to strong CYP enzyme inducers or inhibitors medications or supplements
2. Known liver impairment (defined as >3 times upper limit of normal liver function tests)
3. Significant alcohol intake. This is defined as alcohol intake that exceeds 10 standard drinks a week and/or 4 standard drinks on any one day
4. Patients with known Haemophilic conditions
5. Patients with pro-thrombotic conditions including inherited and acquired thrombophilia, myeloproliferative neoplasm, previous history of venous or arterial thromboembolism
6. Patients currently on anticoagulant and/or antiplatelet therapy or other medications which are deemed by the principal investigator to influence an individual’s coagulation profile (apart from oestrogen therapy)
7. Active malignancy
8. Renal impairment where eGFR <30ml/min/1.73m2
9. Active smokers

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis
In a cross-over study design, 30 trans women without relevant exclusions and on or commencing oestradiol therapy will be recruited from the Monash Health Gender Endocrinology clinic for assessment of hormone levels and global coagulation assays while on oral oestradiol valerate (4 mg, Progynova®) versus sublingual oestradiol (2 mg, Zumenon®®). N=30 will achieve 0.9 power to receive the null hypothesis when the effect size is 0.43 at the significant level 0.05.

The primary endpoint will be analysed for non-inferiority using intention-to-treat and per-protocol principles. Univariate comparison of baseline characteristics will use Pearson Chi-squared test for categorical variables and Pearson’s t-test or Wilcoxon rank-sum test for continuous variables if appropriate. To evaluate the effect of potential confounders, univariate analysis is repeated with demographics variables as covariates, once for each covariate. Comparison of treatments effect with the outcomes will be performed after confounding is regressed. Subgroup analyses will be carried out irrespective of whether significant treatment effect exits on the outcome to help fully characterize the treatment effect. The outcomes in this study are assumed to be missing-at-random (MAR), and will be fixed via imputation. Sensitivity analyses in consideration of a range of plausible alternative assumptions that is relevant to missing primary outcome data will be conducted. Unless specifically stated otherwise, all estimates of treatment effects will be presented with 95% confidence intervals. Significance level in this study is set at 0.05.
Interim analysis will be performed when 10 samples have been collected. Interim analysis will be conducted to accommodate adaptive adjustment of the sample size and review treatment safety and efficacy. Only the primary investigator will have access to the interim data and results. The statistician will remain blinded and work on dummy datasets until the computer codes for statistical analysis are validated. The primary investigator and statistician will regularly review the unblinded data after 5, 10, 15 and 20 participants are enrolled. No formal interim analyses for efficacy are planned.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
14/07/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 44330 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 319259 0
Self funded/Unfunded
Name [1] 319259 0
Country [1] 319259 0
Primary sponsor type
Individual
Name
Rita Upreti - Monash health
Address
Country
Australia
Secondary sponsor category [1] 321732 0
None
Name [1] 321732 0
Address [1] 321732 0
Country [1] 321732 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317837 0
Monash Health Human Research Ethics Committee A
Ethics committee address [1] 317837 0
Ethics committee country [1] 317837 0
Australia
Date submitted for ethics approval [1] 317837 0
11/11/2024
Approval date [1] 317837 0
13/11/2024
Ethics approval number [1] 317837 0
ERM Reference Number: 104644

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142314 0
Dr Rita Upreti - Monash medical Centre, monash health
Address 142314 0
246 Clayton Road, Monash Medical Centre, Clayton VIC 3168
Country 142314 0
Australia
Phone 142314 0
+61 0420468480
Fax 142314 0
Email 142314 0
[email protected]
Contact person for public queries
Name 142315 0
Rita Upreti
Address 142315 0
246 Clayton Road, Monash Medical Centre, Clayton VIC 3168
Country 142315 0
Australia
Phone 142315 0
+61 0420468480
Fax 142315 0
Email 142315 0
[email protected]
Contact person for scientific queries
Name 142316 0
Rita Upreti
Address 142316 0
246 Clayton Road, Monash Medical Centre, Clayton VIC 3168
Country 142316 0
Australia
Phone 142316 0
+61 0420468480
Fax 142316 0
Email 142316 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Informed consent form    Sublingual Oestrogen PICF Version 2.docx
Study protocol    Project description- Coagulation assessment of sublingual oestrogen Version 1.docx
Ethical approval    24-645A HREC Review Only Approval Letter.pdf


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.