Drug InteractionENZA-DNCT03920566
The Effect of ENZAlutamide on the Anti-Xa Levels of Patients Receiving DOACs
An observational study of Drug Interaction, run by Royal Marsden NHS Foundation Trust.
Trial summary
This study aims to determine the nature and significance of the theoretical drug interaction between enzalutamide (a drug used to treat prostate cancer) and the direct-acting oral anticoagulant drugs (DOACs). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Drug Interaction
- What is being tested?
- Anti-Xa level
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- May 2019to Apr 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Patients who are currently taking direct-acting oral anticoagulant drugs who are due to start treatment with enzalutamide for the treatment of prostate cancer.
Who may be able to join
- Male patients aged > 18 years old
- Diagnosis of castrate resistant metastatic prostate cancer
- Due to commence treatment with enzalutamide
- Currently prescribed edoxaban, rivaroxaban or apixaban
- Calculated CrCl (Cockroft \& Gault) > 30ml/min
Who cannot join
- Patients <18 years old
- Due to stop edoxaban/ rivaroxaban / apixaban during study period (i.e. within 4 weeks of recruitment)
- Currently taking other medicines which induce or inhibit P-gp or increase/reduce the effect of apixaban or rivaroxaban (e.g. verapamil, ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, erythromycin (refer to appendix 1 for complete list)
- Currently taking any herbal/complimentary medicines (other than homeopathic products)
- Calculated CrCl (Cockroft \& Gault) <30ml/min
- Severe hepatic impairment (Childs-Pugh class C)
- Lacks capacity, including patients with documented dementia (or psychometric marker e.g. Abbreviated Mental Test Score (AMTS) <7/10) or inability to give informed consent for study participation.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Pilot Study To Investigate the Effect of ENZAlutamide on the Anti-Xa Levels of Patients Receiving Direct-acting Anticoagulants (DOACS) (ENZA-D)
This study aims to determine the nature and significance of the theoretical drug interaction between enzalutamide (a drug used to treat prostate cancer) and the direct-acting oral anticoagulant drugs (DOACs). This will be done in two ways: a laboratory study which will take place at the University of Brighton, and a clinical study in which patients will be identified who are currently taking DOACs and are due to start treatment with enzalutamide. The activity of the DOAC will be monitored using anti-Xa levels before and after commencing treatment with enzalutamide.
Read the detailed description
Enzalutamide is an effective and well-tolerated treatment for advanced prostate cancer. Unfortunately however, enzalutamide can sometimes interact with other medicines that the patient is taking, altering their concentration in the blood-stream. Enzalutamide can do this in two ways: either by increasing the breakdown of a medicine, or by blocking a special protein, called p-glycoprotein, that pumps it out of the body. An example of a medicine whose breakdown is increased by enzalutamide is warfarin. Warfarin is used to prevent, and treat blood clots that have formed in the deep veins of the legs (deep vein thrombosis or DVT) or have become lodged in blood vessels in the lungs (pulmonary embolism or PE). As enzalutamide is known to reduce the effect of warfarin, the manufacturer advises avoiding using the two medicines together. Instead,we can use a new class of medicines called the direct oral anticoagulants, or DOACs.
DOACs have an additional advantage over warfarin in that they do not require regular monitoring with blood tests. We, and other experts in the field believe that there may be a problem using DOACs and enzalutamide together, however scientific evidence suggests that enzalutamide may stop the p-glycoprotein pump from working properly, and alter its ability to pump out a range of medicines. Other evidence suggests that under certain conditions, enzalutamide may actually increase the activity of P-glycoprotein, and reduce the concentration of other medicines in the bloodstream. However, there is no scientific evidence, or evidence from patients, that has looked directly at thecombination of enzalutamide and DOACs together. Because no routine monitoring is carried out with DOACs, we are not sure of the extent of this problem, but the consequences of over or underdosing could be serious.
We have recently generated some preliminary data in our laboratory which has the measured the extent of this interaction, but we need to repeat these experiments before we can draw any firm conclusions from them. In this pilot study, we will explore the potential interaction between enzalutamide and DOACs. First, we will measure the activity of DOACs in patients who are due to start treatment with enzalutamide using a simple, well established blood test. We will then repeat this blood test after the first month of treatment, along with regular blood tests, to determine if there has been a change in the effectiveness of the DOAC. Second, we aim to build uponour laboratory data, and examine whether brief, or prolonged exposure to enzalutamide affects the ability of p-glycoproteinto pump out DOACs.
Our aims are to
- determine if enzalutamide interacts with DOACs in patients recruited from an advanced prostatecancer clinic
- understand in greater detail the nature of any interaction between enzalutamide and DOACs in the laboratory
- assess the feasibility of expanding this study to generate sufficient evidence to make recommendations for clinical practice.
- Conditions
- Drug Interaction
- Being tested
- Anti-Xa level
- Keywords
- Enzalutamide, Anticoagulant Drugs, P-glycoprotein
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-Xa levelOther
Anti-Xa level taken before commencing enzalutamide and repeated after 4 weeks of treatment
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti-Xa level
Difference between anti-Xa levels taken at two time points (baseline and 4-weeks after commencing enzalutamide)
Measured: time 0 and time 4 weeks
Efflux ratio (with enzalutamide)
Difference in efflux ratio for edoxaban/ rivaroxaban / apixaban in the absence/presence of enzalutamide over a range of concentrations
Measured: Each experiment will be conducted over a period of <1 day
Efflux ratio (with enzalutamide and positive control)
Difference in efflux ratio for edoxaban/ rivaroxaban / apixaban in the presence of enzalutamide and a positive control (e.g. verapamil, whilst ensuring appropriate statistical power)
Measured: Each experiment will be conducted over a period of <1 day
Secondary outcomes (3)
Bleeding
Common Terminology Criteria for Adverse Events (various types of bleeding or hemorrhage are listed. The most appropriate will be selected and graded 1-5 where Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
Grade 2=Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.
Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.
Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event
Measured: 4 weeks
Bruising
A finding of injury of the soft tissues or bone characterized by leakage of blood into surrounding tissues. Graded according to Common Terminology Criteria for Adverse Events grades 1-2 where grade 1=localized or in a dependent area and grade 2 = generalize bruising
Measured: 4 weeks
Venous Thromboembolism
Common Terminology Criteria for Adverse Events (various different thromboembolic events are listed. The most appropriate will be selected and graded 1-5 where Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
Grade 2=Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.
Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.
Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2019
- Study startMay 2019 (estimated)
- Primary completionApr 2020 (estimated)
- Study completionApr 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug InteractionStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacy Research UK, University of Brighton
- Responsible party
- Sponsor
- Investigators
- Emma Foreman, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03920566
- Sponsor's protocol ID
- CCR 5039
- Acronym
- ENZA-D
- Status last verified
- Apr 2019
- First submitted
- 27 Mar 2019
- Last updated
- 22 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study To Investigate the Effect of ENZAlutamide on the Anti-Xa Levels of Patients Receiving Direct-acting Anticoagulants (DOACS) (ENZA-D)
- ClinicalTrials.gov ID
- NCT03920566
- Acronym / sponsor ID
- ENZA-D / CCR 5039
- Conditions
- Drug Interaction
- Keywords
- Enzalutamide, Anticoagulant Drugs, P-glycoprotein
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Pharmacy Research UK, University of Brighton
- Study start
- May 2019 (estimated)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Apr 2020 (estimated)
- First posted
- 19 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to determine the nature and significance of the theoretical drug interaction between enzalutamide (a drug used to treat prostate cancer) and the direct-acting oral anticoagulant drugs (DOACs). This will be done in two ways: a laboratory study which will take place at the University of Brighton, and a clinical study in which patients will be identified who are currently taking DOACs and are due to start treatment with enzalutamide. The activity of the DOAC will be monitored using anti-Xa levels before and after commencing treatment with enzalutamide.
Detailed description
Enzalutamide is an effective and well-tolerated treatment for advanced prostate cancer. Unfortunately however, enzalutamide can sometimes interact with other medicines that the patient is taking, altering their concentration in the blood-stream. Enzalutamide can do this in two ways: either by increasing the breakdown of a medicine, or by blocking a special protein, called p-glycoprotein, that pumps it out of the body. An example of a medicine whose breakdown is increased by enzalutamide is warfarin. Warfarin is used to prevent, and treat blood clots that have formed in the deep veins of the legs (deep vein thrombosis or DVT) or have become lodged in blood vessels in the lungs (pulmonary embolism or PE). As enzalutamide is known to reduce the effect of warfarin, the manufacturer advises avoiding using the two medicines together. Instead,we can use a new class of medicines called the direct oral anticoagulants, or DOACs.
DOACs have an additional advantage over warfarin in that they do not require regular monitoring with blood tests. We, and other experts in the field believe that there may be a problem using DOACs and enzalutamide together, however scientific evidence suggests that enzalutamide may stop the p-glycoprotein pump from working properly, and alter its ability to pump out a range of medicines. Other evidence suggests that under certain conditions, enzalutamide may actually increase the activity of P-glycoprotein, and reduce the concentration of other medicines in the bloodstream. However, there is no scientific evidence, or evidence from patients, that has looked directly at thecombination of enzalutamide and DOACs together. Because no routine monitoring is carried out with DOACs, we are not sure of the extent of this problem, but the consequences of over or underdosing could be serious.
We have recently generated some preliminary data in our laboratory which has the measured the extent of this interaction, but we need to repeat these experiments before we can draw any firm conclusions from them. In this pilot study, we will explore the potential interaction between enzalutamide and DOACs. First, we will measure the activity of DOACs in patients who are due to start treatment with enzalutamide using a simple, well established blood test. We will then repeat this blood test after the first month of treatment, along with regular blood tests, to determine if there has been a change in the effectiveness of the DOAC. Second, we aim to build uponour laboratory data, and examine whether brief, or prolonged exposure to enzalutamide affects the ability of p-glycoproteinto pump out DOACs.
Our aims are to
- determine if enzalutamide interacts with DOACs in patients recruited from an advanced prostatecancer clinic
- understand in greater detail the nature of any interaction between enzalutamide and DOACs in the laboratory
- assess the feasibility of expanding this study to generate sufficient evidence to make recommendations for clinical practice.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who are currently taking direct-acting oral anticoagulant drugs who are due to start treatment with enzalutamide for the treatment of prostate cancer.
Key inclusion criteria (5 listed)
- Male patients aged > 18 years old
- Diagnosis of castrate resistant metastatic prostate cancer
- Due to commence treatment with enzalutamide
- Currently prescribed edoxaban, rivaroxaban or apixaban
- Calculated CrCl (Cockroft \& Gault) > 30ml/min
Key exclusion criteria (7 listed)
- Patients <18 years old
- Due to stop edoxaban/ rivaroxaban / apixaban during study period (i.e. within 4 weeks of recruitment)
- Currently taking other medicines which induce or inhibit P-gp or increase/reduce the effect of apixaban or rivaroxaban (e.g. verapamil, ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, erythromycin (refer to appendix 1 for complete list)
- Currently taking any herbal/complimentary medicines (other than homeopathic products)
- Calculated CrCl (Cockroft \& Gault) <30ml/min
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-Xa levelAnti-Xa level taken before commencing enzalutamide and repeated after 4 weeks of treatment | Other | – |
Primary outcome
Anti-Xa level
Time frame: time 0 and time 4 weeks
Difference between anti-Xa levels taken at two time points (baseline and 4-weeks after commencing enzalutamide)
Efflux ratio (with enzalutamide)
Time frame: Each experiment will be conducted over a period of <1 day
Difference in efflux ratio for edoxaban/ rivaroxaban / apixaban in the absence/presence of enzalutamide over a range of concentrations
Efflux ratio (with enzalutamide and positive control)
Time frame: Each experiment will be conducted over a period of <1 day
Difference in efflux ratio for edoxaban/ rivaroxaban / apixaban in the presence of enzalutamide and a positive control (e.g. verapamil, whilst ensuring appropriate statistical power)
3 secondary outcomes
Bleeding
Time frame: 4 weeks
Bruising
Time frame: 4 weeks
Venous Thromboembolism
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emma Foreman principal investigator
Royal Marsden NHS Foundation Trust
Questions about this trial
What is this clinical trial studying?
An observational study of Drug Interaction, run by Royal Marsden NHS Foundation Trust.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Emma Foreman (0208 6426011 ext. 1067, Emma.Foreman@rmh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anti-Xa level (time frame: time 0 and time 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2019; AzTrials last refreshed its copy on 8 Nov 2026.