Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000542796
Ethics application status
Approved
Date submitted
23/03/2022
Date registered
6/04/2022
Date last updated
11/01/2024
Date data sharing statement initially provided
6/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring the activity of pseudoephedrine in treating retrograde ejaculation following retroperitoneal lymph node dissection (RPLND) in survivors of testicular cancer - Part B
Scientific title
Exploring the activity of pseudoephedrine in treating retrograde ejaculation following retroperitoneal lymph node dissection (RPLND) in survivors of testicular cancer - Part B
Secondary ID [1] 306721 0
PMC81808
Universal Trial Number (UTN)
Trial acronym
PREPARE
Linked study record
This study is a follow-up study to ACTRN12622000537752

Health condition
Health condition(s) or problem(s) studied:
Testicular cancer 325701 0
Retrograde ejaculation 325702 0
Retroperitoneal node dissection 325832 0
Condition category
Condition code
Cancer 323050 323050 0 0
Testicular
Surgery 323155 323155 0 0
Other surgery
Renal and Urogenital 323157 323157 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PREPARE Part B is a prospective, phase 2, single-arm, open-label study building upon the information gathered in Part A. It will enrol participants with retrograde ejaculation and explore an intervention to help treat the condition. Eligible participants in Part B will receive a short course of pseudoephedrine (60mg every 6 hours for 24 hours administered orally as a tablet, followed by repeat administration at 0600hrs and 30-60 minutes prior to ejaculation) and undergo repeat semen and post-ejaculatory urine analysis to explore the efficacy of this treatment. Participant medication diaries will be completed. After this ~30-hour period, pseudoephedrine is ceased.

Additionally, participants in Part B will complete health-related quality of life questionnaires if not performed in Part A and will also be invited to participate in an optional, semi-structured interview.
Intervention code [1] 323169 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 330812 0
Proportion of participants with total sperm count of antegrade ejaculate of at least 39 million (5th centile) using semen analysis following treatment with pseudoephedrine.
Timepoint [1] 330812 0
1 day post-pseudoephedrine commencement
Secondary outcome [1] 407650 0
Proportion of participants with ejaculate volume of at least 1.5mL (5th centile) using semen analysis following treatment with pseudoephedrine.
Timepoint [1] 407650 0
1 day post-pseudoephedrine commencement
Secondary outcome [2] 407651 0
Change in sperm motility from pre- to post-treatment, analysed by semen analysis
Timepoint [2] 407651 0
1 day post-pseudoephedrine commencement
Secondary outcome [3] 407653 0
Adverse events, defined by Common Terminology Criteria for Adverse Events, version 4.03, for example allergy, urinary retention, palpitation, hypertension.
Timepoint [3] 407653 0
Days 0-28 post-pseudoephedrine commencement; collected formally 28 days after commencement of pseudoephedrine and ad hoc in event of clinical need or SAE. Participants will be encouraged to report any side effects or concerns to the study team prior to routine collection of this data at the Day 28 visit.
Secondary outcome [4] 408018 0
Change in sperm morphology from pre- to post-pseudoephedrine treatment, analysed by semen analysis.
Timepoint [4] 408018 0
1 day post-pseudoephedrine commencement
Secondary outcome [5] 408020 0
Change in post-ejaculatory urine sperm count between pre- and post-pseudoephedrine treatment, analysed by semen analysis
Timepoint [5] 408020 0
1 day post-pseudoephedrine commencement

Eligibility
Key inclusion criteria
Participants must meet all the following criteria for study entry:
1. Participant has provided written, informed consent OR electronic, informed consent sighted by an investigator, on Telehealth.
2. Males greater than or equal to 18 years at time of informed consent.
3. Histologically confirmed testicular germ cell tumour (based on archival tissue report)
4. Retroperitoneal lymph node dissection for management of testicular cancer at least six months prior to consent.
5. Confirmed retrograde ejaculation on basis of semen and post-ejaculatory urine analysis, where retroperitoneal lymph node dissection is the likely cause in the opinion of the investigator.
6. Participant is willing and able to comply with the protocol for the duration of the study including treatment, and scheduled visits and examination including follow up.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Participants who meet any of the following criteria will be excluded from study entry:
1. Currently receiving treatment or planning to receive treatment within two months (i.e., surgery, chemotherapy, radiotherapy) for testicular cancer (or other malignancy).
2. Contraindications to pseudoephedrine, including allergy to pseudoephedrine or components, uncontrolled hypertension, poorly controlled diabetes mellitus, seizure disorder, closed angle glaucoma, existing ischaemic heart disease, urinary retention; or other conditions in the opinion of the investigator would pose subject undue risk.
3. Currently receiving testosterone replacement therapy (or within last 12 weeks if receiving long-acting preparation).
4. Known medical condition or other issue that in the opinion of the investigator, that would affect adherence to study requirements.

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
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Baseline demographic and clinical characteristics collected during screening in PREPARE will be presented in tabular format and analysed using descriptive statistics and Student t-tests, where comparisons between groups are required. A p value of <0.05 will define statistical significance. Treatment-related adverse events will also be documented in text or tables, as applicable.

For Part A, the primary outcome will be summarised descriptively with the prevalence of retrograde ejaculation defined as the number of participants reporting retrograde ejaculation, of all men recruited to this study. Secondary outcomes will also be summarised descriptively, including mean and median, where relevant. HRQoL measures will be summarised using means and 95% confidence intervals of the means of men experiencing (or not) retrograde ejaculation. An analysis of covariance will be fitted to determine impact of retrograde ejaculation on HRQoL and time from RPLND. These will be compiled with any additional HRQoL questionnaire data obtained from participants entering PREPARE Part B (who did not participate in Part A).

For Part B, The primary endpoint will be analysed using the one-sample exact binomial test of proportion against a null hypothesis of the proportion being 0.1 or less. Change in continuous outcomes, such as ejaculate volume and sperm count, will be analysed using multilevel mixed-effects linear regression using a random intercepts and slopes model. Predictors of continuous outcomes such as ejaculate volume will be analysed using linear regression. Predictors of categorical outcomes such as partial versus complete retrograde ejaculation will be analysed using logistic regression at the two-sided 0.05 significance level.
HRQoL measures will be summarised using means and 95% confidence intervals of the means of men experiencing (or not) retrograde ejaculation. An analysis of covariance will be fitted to determine impact of retrograde ejaculation on HRQoL and time from RPLND using all HRQoL questionnaire data from Part A and B. Thematic analysis of semi-structured interviews exploring the experiences of individuals with retrograde ejaculation will be undertaken in accordance with established methods

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/08/2022
Actual
6/09/2022
Date of last participant enrolment
Anticipated
30/06/2023
Actual
11/08/2023
Date of last data collection
Anticipated
28/07/2023
Actual
5/09/2023
Sample size
Target
30
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 21992 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 37093 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 311049 0
Charities/Societies/Foundations
Name [1] 311049 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Below the Belt Research Fund
Country [1] 311049 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
Office of Cancer Research, Peter MacCallum Cancer Centre
305 Grattan St, Melbourne, VIC 3000
Country
Australia
Secondary sponsor category [1] 312382 0
None
Name [1] 312382 0
Address [1] 312382 0
Country [1] 312382 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310597 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 310597 0
Ethics committee country [1] 310597 0
Australia
Date submitted for ethics approval [1] 310597 0
03/12/2021
Approval date [1] 310597 0
10/03/2022
Ethics approval number [1] 310597 0
21/231

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

Contacts
Principal investigator
Name 118210 0
A/Prof Ben Tran
Address 118210 0
Peter MacCallum Cancer Centre
305 Grattan St, Melbourne, VIC, 3000.
Country 118210 0
Australia
Phone 118210 0
+61 385597902
Fax 118210 0
Email 118210 0
[email protected]
Contact person for public queries
Name 118211 0
Ben Tran
Address 118211 0
Peter MacCallum Cancer Centre
305 Grattan St, Melbourne, VIC, 3000.
Country 118211 0
Australia
Phone 118211 0
+61 385597902
Fax 118211 0
Email 118211 0
[email protected]
Contact person for scientific queries
Name 118212 0
Ben Tran
Address 118212 0
Peter MacCallum Cancer Centre
305 Grattan St, Melbourne, VIC, 3000.
Country 118212 0
Australia
Phone 118212 0
+61 385597902
Fax 118212 0
Email 118212 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 collected during the trial may be shared in discussion with the Sponsor, provided individual participants have provided consent for sharing of their data.
When will data be available (start and end dates)?
After final analysis and publication of results of PREPARE and for up to 5 years after this time.
Available to whom?
To other collaborators or research parties.
Available for what types of analyses?
Ethically-approved research.
How or where can data be obtained?
Email the Principal Investigator ([email protected]) for approval of the Sponsor


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.