Healthy VolunteersPhase 4NCT02875028
Vorapaxar in the Human Endotoxemia Model
A Phase 4 study testing Vorapaxar and LPS in people with Healthy Volunteers, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Vorapaxar is a recently approved protease activated receptor - 1 (PAR-1) inhibitor. Platelet inhibition may also exert positive results on coagulation activation and may beneficially influence the inflammatory response. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Vorapaxar and LPS
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteAustria
- Study dates
- Jun 2016to 30 Nov 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- ≥18 years of age
- ≥60 kg bodyweight
- Normal findings in medical history and physical examination unless the investigator considers the abnormality to be clinically irrelevant
- Normal laboratory values unless the investigator considers abnormalities to be clinically irrelevant
- Willingness to comply with the trial's safety demands (to refrain from excessive sporting activities two weeks after Vorapaxar intake, i.e. full contact sports, climbing, mountain biking etc.)
- Ability to understand the purpose and nature of the study, as well as the associated risks No planned surgeries or other medical interventions in the planned study period
Who cannot join
- Intake of any drugs that may interfere with the trial's endpoints or drugs (i.e. platelet inhibitors, anticoagulants, CYP3A4 inhibitors, NSAIDs, selective serotonin reuptake inhibitors, selective noradrenaline and serotonin reuptake inhibitors)
- Positive results of HIV or hepatitis virology
- Acute illness with systemic inflammatory reactions
- Known allergies, hypersensitivities or intolerances to any of the used substances
- Acute or recent bleeding episodes, increased risk of bleeding at the discretion of the investigator
- History of stroke, transient ischemic attacks or intracerebral hemorrhage
Show all 10Show fewer
- Known coagulation or platelet disorders
- Participation in an LPS trial within 6 weeks of the first study day
- Severe liver or kidney dysfunction
- Pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country.
Austria1 site
Department of Clinical Pharmacology, Medical University of Vienna
Vienna, 1090
About this study
Official title: Vorapaxar in the Human Endotoxemia Model A Randomized, Double-Blind, Crossover Study
Vorapaxar is a recently approved protease activated receptor - 1 (PAR-1) inhibitor. Platelet inhibition may also exert positive results on coagulation activation and may beneficially influence the inflammatory response. Since vorapaxar is the first available substance of a new class of platelet inhibitors its effects on the human coagulation system and the inflammatory response will be assessed in the well-established human endotoxemia model.
Read the detailed description
Vorapaxar is a novel platelet inhibitor inhibiting PAR-1. It is the first available substance of a new class of platelet inhibitors blocking the activation of platelets via thrombin or thrombin receptor activating peptides via PAR-1. As platelets contribute to the coagulation activation, i.e. by providing the surface for the assembly of the Tenase complex, and furthermore to the inflammatory response by releasing their stored granula containing promotors of both, inflammation and coagulation, we want to assess the effects of vorapaxar on these in the human endotoxemia model. Sixteen healthy volunteers will be included in this randomized, double-blind, placebo-controlled, single center, crossover trial with a washout period of 8 weeks. This wash out period was chosen based on the long elimination half-life of vorapaxar and to prevent any carry-over effects. After intake of 10mg vorapaxar (-24h) the degree of platelet inhibition will be assessed by whole bood aggregometry and, in case of insufficient platelet inhibition, subjects may receive another 10mg of vorapaxar. A bolus of 2ng/kg bodyweight lipopolysaccharide (LPS) will be infused and blood sampling will be performed at pre-defined time-points. After the washout-period the respective other treatment will be given to subjects.
- Conditions
- Healthy Volunteers
- Being tested
- Vorapaxar, Placebo, LPS
- Keywords
- Coagulations, Platelets, Inflammation, endotoxemia, vorapaxar
- Medical subject headings
- Inflammation, Endotoxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorapaxarDrug
10mg-20mg vorapaxar to achieve >80% thrombin-receptor activated peptide-6 (TRAP) induced platelet inhibition
PlaceboDrug
Also called capsules consisting of lactose-starch
LPSOther
Also called Lipopolysaccharide
2ng/kg Lipopolysaccharide as a bolus infusion
| Study group | Role | What they receive |
|---|---|---|
| Vorapaxar | Experimental | subjects will be treated with 4x2,5mg vorapaxar in empty lactose-starch capsules Receives: Drug: Vorapaxar; Other: LPS |
| Placebo | Placebo comparator | subjects will be treated with 4 empty lactose-starch capsules Receives: Drug: Placebo; Other: LPS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Prothrombin Fragments F1+2
prothrombin fragment F1+2 concentrations, individual maxima were compared between both study periods
Measured: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
Secondary outcomes (11)
Protease Activated Receptor (PAR)-1 Expression on Platelets
Protease Activated Receptor (PAR)-1 expression on platelets was measured by flow cytometric analysis. The change in protease activated receptor (PAR)-1 expression over time was assessed. The ratio of protease activated receptor (PAR)-1 expression from baseline to 4h was the main parameter of interest and is presented here.
Since the presented data are ratios, the arbitrary unit is "fold". Otherwise flow cytometric data is presented as "hits" during the analysis.
Measured: Time points for evaluation were: baseline, 0h, 4h, 24h
Thrombin-Antithrombin Complexes
Thrombin-Antithrombin Complexes were quantified using commercially available "ELISA" assays.
The individual maxima during the study periods were compared.
Measured: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
Plasmin-Antiplasmin Complexes
Plasmin-Antiplasmin Complexes were quantified using commercially available "ELISA" assays. Individual maxima during both study periods were compared.
Measured: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
E-Selectin
E-Selectin concentrations were quantified using commercially available "ELISA" assays, individual maxima were compared between both study periods
Measured: Time points for evaluation were baseline, 2h, 4h, 6h, 24h after LPS administration
Von Willebrand Factor
von Willebrand factor concentrations were measured by commercially available "ELISA" assays, individual maxima were compared between both study periods. The result of this assay are % of "normal" (100%) for this specific assay. The unit therefore is %.
Measured: Time points for evaluation were baseline, 2h, 4h, 6h, 24h after LPS administration
P-Selectin
P-Selectin is quantified using commercially available "ELISA" assays, individual maxima were compared between both study periods.
Measured: Time points for evaluation were baseline, 2h, 4h, 6h 24h after LPS administration
Interleukin 6
interleukin-6 concentrations were measured by commercially available "ELISA" assays, individual maxima were compared between both study periods
Measured: Time points for evaluation were baseline, 2h, 4h, 6h 24h after LPS administration
Tumor Necrosis Factor Alpha
tumor necrosis factor alpha concentrations were measured using commercially available "ELISA" assays, individual maxima were compared between both study periods
Measured: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
C-reactive Protein
C-reactive protein levels were measured in the certified central laboratory of the General Hospital, 24h values were compared with each other
Measured: Time points for evaluation were: baseline, and 24h after LPS administration
Platelet Factor 4
platelet factor 4 concentrations were quantified by "ELISA", individual maxima were compared between both study periods
Measured: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
Thrombomodulin
thrombomodulin concentrations were measured by commercially available "ELISA" assays, individual maxima were compared between both study periods
Measured: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2016 (estimated)
- Study startJun 2016
- Primary completion30 Nov 2016
- Study completion30 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bernd Jilma, Medical University of Vienna
- Investigators
- Bernd Jilma, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02875028
- Sponsor's protocol ID
- LPS_Vorapaxar_1.1
- Status last verified
- Dec 2019
- First submitted
- 27 Jun 2016
- Last updated
- 10 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: A manuscript will be published in a peer-reviewed journal, individual data will not be presented unless directly requested from the PI (anonymized data may be made publicly available)
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vorapaxar in the Human Endotoxemia Model A Randomized, Double-Blind, Crossover Study
- ClinicalTrials.gov ID
- NCT02875028
- Acronym / sponsor ID
- LPS_Vorapaxar_1.1
- Conditions
- Healthy Volunteers
- Keywords
- Coagulations, Platelets, Inflammation, endotoxemia, vorapaxar
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Jun 2016 (actual)
- Primary completion
- 30 Nov 2016 (actual)
- Study completion
- 30 Nov 2016 (actual)
- First posted
- 23 Aug 2016 (estimated)
- Results
- Posted 10 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vorapaxar is a recently approved protease activated receptor - 1 (PAR-1) inhibitor. Platelet inhibition may also exert positive results on coagulation activation and may beneficially influence the inflammatory response. Since vorapaxar is the first available substance of a new class of platelet inhibitors its effects on the human coagulation system and the inflammatory response will be assessed in the well-established human endotoxemia model.
Detailed description
Vorapaxar is a novel platelet inhibitor inhibiting PAR-1. It is the first available substance of a new class of platelet inhibitors blocking the activation of platelets via thrombin or thrombin receptor activating peptides via PAR-1. As platelets contribute to the coagulation activation, i.e. by providing the surface for the assembly of the Tenase complex, and furthermore to the inflammatory response by releasing their stored granula containing promotors of both, inflammation and coagulation, we want to assess the effects of vorapaxar on these in the human endotoxemia model. Sixteen healthy volunteers will be included in this randomized, double-blind, placebo-controlled, single center, crossover trial with a washout period of 8 weeks. This wash out period was chosen based on the long elimination half-life of vorapaxar and to prevent any carry-over effects. After intake of 10mg vorapaxar (-24h) the degree of platelet inhibition will be assessed by whole bood aggregometry and, in case of insufficient platelet inhibition, subjects may receive another 10mg of vorapaxar. A bolus of 2ng/kg bodyweight lipopolysaccharide (LPS) will be infused and blood sampling will be performed at pre-defined time-points. After the washout-period the respective other treatment will be given to subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vorapaxar | Experimental | Drug: Vorapaxar, Other: LPSsubjects will be treated with 4x2,5mg vorapaxar in empty lactose-starch capsules |
| Placebo | Placebo comparator | Drug: Placebo, Other: LPSsubjects will be treated with 4 empty lactose-starch capsules |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- ≥18 years of age
Key exclusion criteria (10 listed)
- Intake of any drugs that may interfere with the trial's endpoints or drugs (i.e. platelet inhibitors, anticoagulants, CYP3A4 inhibitors, NSAIDs, selective serotonin reuptake inhibitors, selective noradrenaline and serotonin reuptake inhibitors)
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 |
|---|---|---|
| Vorapaxar10mg-20mg vorapaxar to achieve >80% thrombin-receptor activated peptide-6 (TRAP) induced platelet inhibition | Drug | Vorapaxar |
| PlaceboAlso: capsules consisting of lactose-starch | Drug | Placebo |
| LPSAlso: Lipopolysaccharide2ng/kg Lipopolysaccharide as a bolus infusion | Other | Placebo, Vorapaxar |
Primary outcome
Changes in Prothrombin Fragments F1+2
Time frame: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
prothrombin fragment F1+2 concentrations, individual maxima were compared between both study periods
11 secondary outcomes
Protease Activated Receptor (PAR)-1 Expression on Platelets
Time frame: Time points for evaluation were: baseline, 0h, 4h, 24h
Thrombin-Antithrombin Complexes
Time frame: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
Plasmin-Antiplasmin Complexes
Time frame: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
E-Selectin
Time frame: Time points for evaluation were baseline, 2h, 4h, 6h, 24h after LPS administration
Von Willebrand Factor
Time frame: Time points for evaluation were baseline, 2h, 4h, 6h, 24h after LPS administration
P-Selectin
Time frame: Time points for evaluation were baseline, 2h, 4h, 6h 24h after LPS administration
Interleukin 6
Time frame: Time points for evaluation were baseline, 2h, 4h, 6h 24h after LPS administration
Tumor Necrosis Factor Alpha
Time frame: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
C-reactive Protein
Time frame: Time points for evaluation were: baseline, and 24h after LPS administration
Platelet Factor 4
Time frame: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
Thrombomodulin
Time frame: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. A manuscript will be published in a peer-reviewed journal, individual data will not be presented unless directly requested from the PI (anonymized data may be made publicly available)
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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.
Bernd Jilma, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vorapaxar and LPS in people with Healthy Volunteers, run by Medical University of Vienna at 1 site in Austria.
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 6 inclusion and 10 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: finished, as of the sponsor's last update on 10 Jan 2020. 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 Austria. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in Prothrombin Fragments F1+2 (time frame: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h). 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 10 Jan 2020.