HivPhase 1IMPACT/RNCT03054207
Impact of Antiretroviral Treatment on Pharmacokinetics and Pharmacodynamics of Thienopyridines in Healthy Volunteers and HIV Patients
A Phase 1 study testing Clopidogrel 300Mg Tablet and Prasugrel 60Mg in people with Hiv, run by Jules Desmeules at 1 site in Switzerland.
Trial summary
HIV patients are at particular risk to develop cardiovascular disease (CVD) as they exhibit multiple risk factors by the nature of their pathology. In addition, the long term exposition to antiretroviral drugs has been associated to an increased risk for CVD. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hiv
- What is being tested?
- Clopidogrel 300Mg Tablet and Prasugrel 60Mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jun 2015to Apr 2017
- Phase
- Phase 1
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy males >18 years
- Understanding of French language and able to give an inform consent
- Anti-HIV therapy with ritonavir or cobicistat (for HIV group)
- Stable antiretroviral treatment since at least 2 weeks (for HIV group)
- Viremia <100 copies/ml (for HIV group)
Who cannot join
- renal failure: calculated creatinine Clearance (cockcroft) < 50ml/min
- hepatic impairment (ASAT, ALAT, bilirubin, gamma-GT more than 2-fold increase)
- smoker >1 pack/day
- hypersensitivity to any of the drugs used
- intake of any drug or particular food (grapefruit) that can affect CYP activities inhibitors (in the last 10 days before the start of the study or 4 half-life after the last intake)
- pathologies or drugs associated with an increased bleeding risk such as aspirin, non-steroidal anti-inflammatory drugs, steroids and serotonin reuptake inhibitors (in the last 10 days before the start of the study or 4 half-life after the last intake)
- bleeding familial history or antecedent or haemorrhagic disease
Trial locations and contacts
1 site in 1 country.
About this study
HIV patients are at particular risk to develop cardiovascular disease (CVD) as they exhibit multiple risk factors by the nature of their pathology. In addition, the long term exposition to antiretroviral drugs has been associated to an increased risk for CVD. HIV patients can thus potentially receive antiplatelet therapy concomitantly with their antiretroviral treatment. Clopidogrel and prasugrel are thienopyridine antiplatelet agents indicated to prevent the recurrence of ischemic events after coronary arteries stenting. These pro-drugs are mainly bioactivated by cytochromes P450 (CYP) 3A and 2B6 for prasugrel and CYP2C19, CYP3A and CYP2B6 for clopidogrel. Ritonavir is commonly used to "boost" the bioavailability of other HIV drugs through inhibition of CYP3A4 as well as CYP2B6 and CYP2C9. This interaction could therefore reduce clopidogrel and prasugrel efficacy by reducing the formation of their active metabolites. The aim of the present study is to assess the potential drug-drug interaction between clopidogrel/prasugrel and ritonavir. Two groups of 12 male subjects will be constituted (12 HIV patients under ritonavir boosted therapy and 12 healthy volunteers) in a randomized cross-over clinical trial. All subjects will also be genotyped for the CYP2C19. The pharmacokinetics of clopidogrel active metabolite and prasugrel active metabolite will be assessed. Furthermore, the pharmacodynamic response will be evaluated by two gold standard platelet inhibition tests, namely VAsodilator-Stimulated Phosphoprotein Assay (VASP) and VerifyNow® assays. The primary endpoint of this study is to compare the pharmacodynamic response to clopidogrel and prasugrel in HIV patients to that of healthy volunteers.
- Conditions
- Hiv
- Being tested
- Clopidogrel 300Mg Tablet, Prasugrel 60Mg
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clopidogrel 300Mg TabletDrug
Prasugrel 60MgDrug
| Study group | Role | What they receive |
|---|---|---|
| HIV clopidogrel | Experimental | clopidogrel 300 mg single dose oral route Receives: Drug: Clopidogrel 300Mg Tablet |
| HIV prasugrel | Experimental | prasugrel 60 mg single dose oral route Receives: Drug: Prasugrel 60Mg |
| Control clopidogrel | Active comparator | clopidogrel 300 mg single dose oral route Receives: Drug: Clopidogrel 300Mg Tablet |
| Control prasugrel | Active comparator | prasugrel 60 mg single dose oral route Receives: Drug: Prasugrel 60Mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of Platelet Reactivity Index between HIV patients and healthy volunteers
assess the effect of antiretroviral therapies on the response to antiplatelet treatment
Measured: 4hr
Secondary outcomes (6)
Comparison of platelet inhibition between HIV patients and healthy volunteers
Measured: 4hr
Comparison of AUC of plasmatic concentrations of prasugrel and clopidogrel between HIV patients and healthy volunteers
Measured: 4 hr
Comparison of Cmax of prasugrel and clopidogrel between HIV patients and healthy volunteers
Measured: 4 hr
Comparison of Tmax of plasmatic concentrations of prasugrel and clopidogrelpatients and healthy between HIV patients and healthy volunteersvolunteers
Measured: 4 hr
Comparison of Half life of prasugrel and clopidogrel between HIV patients and healthy volunteers
Measured: 4 hr
Comparison of Clearance of prasugrel and clopidogrel between HIV patients and healthy volunteers
Measured: 4 hr
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2017
- Study startJun 2015
- Primary completionApr 2017
- Study completionApr 2017
Why it stopped: difficulty to recruit
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HivStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jules Desmeules
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jules Desmeules, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03054207
- Sponsor's protocol ID
- 13-096
- Acronym
- IMPACT/R
- Status last verified
- Feb 2017
- First submitted
- 6 Feb 2017
- Last updated
- 11 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Antiretroviral Treatment on Pharmacokinetics and Pharmacodynamics of Thienopyridines in Healthy Volunteers and HIV Patients
- ClinicalTrials.gov ID
- NCT03054207
- Acronym / sponsor ID
- IMPACT/R / 13-096
- Conditions
- Hiv
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: difficulty to recruit
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Jules DesmeulesUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 15 Feb 2017 (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.
HIV patients are at particular risk to develop cardiovascular disease (CVD) as they exhibit multiple risk factors by the nature of their pathology. In addition, the long term exposition to antiretroviral drugs has been associated to an increased risk for CVD. HIV patients can thus potentially receive antiplatelet therapy concomitantly with their antiretroviral treatment. Clopidogrel and prasugrel are thienopyridine antiplatelet agents indicated to prevent the recurrence of ischemic events after coronary arteries stenting. These pro-drugs are mainly bioactivated by cytochromes P450 (CYP) 3A and 2B6 for prasugrel and CYP2C19, CYP3A and CYP2B6 for clopidogrel. Ritonavir is commonly used to "boost" the bioavailability of other HIV drugs through inhibition of CYP3A4 as well as CYP2B6 and CYP2C9. This interaction could therefore reduce clopidogrel and prasugrel efficacy by reducing the formation of their active metabolites. The aim of the present study is to assess the potential drug-drug interaction between clopidogrel/prasugrel and ritonavir. Two groups of 12 male subjects will be constituted (12 HIV patients under ritonavir boosted therapy and 12 healthy volunteers) in a randomized cross-over clinical trial. All subjects will also be genotyped for the CYP2C19. The pharmacokinetics of clopidogrel active metabolite and prasugrel active metabolite will be assessed. Furthermore, the pharmacodynamic response will be evaluated by two gold standard platelet inhibition tests, namely VAsodilator-Stimulated Phosphoprotein Assay (VASP) and VerifyNow® assays. The primary endpoint of this study is to compare the pharmacodynamic response to clopidogrel and prasugrel in HIV patients to that of healthy volunteers.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HIV clopidogrel | Experimental | Drug: Clopidogrel 300Mg Tabletclopidogrel 300 mg single dose oral route |
| HIV prasugrel | Experimental | Drug: Prasugrel 60Mgprasugrel 60 mg single dose oral route |
| Control clopidogrel | Active comparator | Drug: Clopidogrel 300Mg Tabletclopidogrel 300 mg single dose oral route |
| Control prasugrel | Active comparator | Drug: Prasugrel 60Mgprasugrel 60 mg single dose oral route |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Healthy males >18 years
- Understanding of French language and able to give an inform consent
- Anti-HIV therapy with ritonavir or cobicistat (for HIV group)
- Stable antiretroviral treatment since at least 2 weeks (for HIV group)
- Viremia <100 copies/ml (for HIV group)
Key exclusion criteria (7 listed)
- renal failure: calculated creatinine Clearance (cockcroft) < 50ml/min
- hepatic impairment (ASAT, ALAT, bilirubin, gamma-GT more than 2-fold increase)
- smoker >1 pack/day
- hypersensitivity to any of the drugs used
- intake of any drug or particular food (grapefruit) that can affect CYP activities inhibitors (in the last 10 days before the start of the study or 4 half-life after the last intake)
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 |
|---|---|---|
| Clopidogrel 300Mg Tablet | Drug | Control clopidogrel, HIV clopidogrel |
| Prasugrel 60Mg | Drug | Control prasugrel, HIV prasugrel |
Primary outcome
Comparison of Platelet Reactivity Index between HIV patients and healthy volunteers
Time frame: 4hr
assess the effect of antiretroviral therapies on the response to antiplatelet treatment
6 secondary outcomes
Comparison of platelet inhibition between HIV patients and healthy volunteers
Time frame: 4hr
Comparison of AUC of plasmatic concentrations of prasugrel and clopidogrel between HIV patients and healthy volunteers
Time frame: 4 hr
Comparison of Cmax of prasugrel and clopidogrel between HIV patients and healthy volunteers
Time frame: 4 hr
Comparison of Tmax of plasmatic concentrations of prasugrel and clopidogrelpatients and healthy between HIV patients and healthy volunteersvolunteers
Time frame: 4 hr
Comparison of Half life of prasugrel and clopidogrel between HIV patients and healthy volunteers
Time frame: 4 hr
Comparison of Clearance of prasugrel and clopidogrel between HIV patients and healthy volunteers
Time frame: 4 hr
Results and safety
The study was stopped early (reason given: difficulty to recruit). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2017.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clopidogrel 300Mg Tablet and Prasugrel 60Mg in people with Hiv, run by Jules Desmeules at 1 site in Switzerland.
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: stopped early, as of the sponsor's last update on 11 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: difficulty to recruit). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of Platelet Reactivity Index between HIV patients and healthy volunteers (time frame: 4hr). 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 11 Sep 2017.