A Phase 4 interventional study of Vorapaxar and Placebo in Healthy Volunteers, sponsored by Medical University of Vienna. Completed at 1 site in Austria. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-01-10.
Sponsored by Medical University of Vienna · Phase 4, Interventional, and Treatment
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.
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.
81 studies on the registry are indexed under Endotoxemia; 7 are open to participants now.
This study's enrollment of 16 is below the median of 31 across 70 interventional studies indexed under Endotoxemia.
Browse Endotoxemia studies →Medical University of Vienna is the lead sponsor of 1,109 studies on the registry; 184 are open to participants now.
Compared within Endotoxemia, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Inflammation. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
≥18 years of age
Exclusion Criteria:
Intake of any drugs that may interfere with the trial's endpoints or drugs (i.e. inhibitors, anticoagulants, inhibitors, NSAIDs, selective serotonin reuptake inhibitors, selective noradrenaline and serotonin reuptake inhibitors)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
subjects will be treated with 4x2,5mg vorapaxar in empty lactose-starch capsules
Drug: Vorapaxar · Other: LPS
subjects will be treated with 4 empty lactose-starch capsules
Drug: Placebo · Other: LPS
10mg-20mg vorapaxar to achieve \>80% thrombin-receptor activated peptide-6 (TRAP) induced platelet inhibition
Also known as: capsules consisting of lactose-starch
2ng/kg Lipopolysaccharide as a bolus infusion
Also known as: Lipopolysaccharide
Changes in Prothrombin Fragments F1+2
prothrombin fragment F1+2 concentrations, individual maxima were compared between both study periods
Time frame: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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 %.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Time points for evaluation were: baseline, 0h, 2h, 4h, 6h, 24h
16 healthy volunteers participated in this crossover trial.
| Milestone | Vorapaxar, Then Placebo | Placebo First, Then Vorapaxar |
|---|---|---|
| Started | 8 | 8 |
| Completed | 8 | 8 |
| Not completed | 0 | 0 |
| Milestone | Vorapaxar, Then Placebo | Placebo First, Then Vorapaxar |
|---|---|---|
| Started | 8 | 8 |
| Completed | 8 | 7 |
| Not completed | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Milestone | Vorapaxar, Then Placebo | Placebo First, Then Vorapaxar |
|---|---|---|
| Started | 8 | 7 |
| Completed | 8 | 7 |
| Not completed | 0 | 0 |
prothrombin fragment F1+2 concentrations, individual maxima were compared between both study periods
| pmol/L | Vorapaxar | Placebo |
|---|---|---|
| Changes in Prothrombin Fragments F1+2 | 1315 (835 to 1800) | 2530 (1175 to 3895) |
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.
| fold | Vorapaxar | Placebo |
|---|---|---|
| Protease Activated Receptor (PAR)-1 Expression on Platelets | 0.85 (0.78 to 1.01) | 0.83 (0.77 to 0.89) |
Thrombin-Antithrombin Complexes were quantified using commercially available "ELISA" assays. The individual maxima during the study periods were compared.
| µg/L | Vorapaxar | Placebo |
|---|---|---|
| Thrombin-Antithrombin Complexes | 17.4 (8.06 to 25.1) | 32.3 (13.9 to 55.2) |
Plasmin-Antiplasmin Complexes were quantified using commercially available "ELISA" assays. Individual maxima during both study periods were compared.
| µg/L | Vorapaxar | Placebo |
|---|---|---|
| Plasmin-Antiplasmin Complexes | 745 (625 to 1227) | 1437 (764 to 1951) |
E-Selectin concentrations were quantified using commercially available "ELISA" assays, individual maxima were compared between both study periods
| ng/mL | Vorapaxar | Placebo |
|---|---|---|
| E-Selectin | 43.5 (39.85 to 89) | 76.5 (48 to 92.5) |
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 %.
| % of "normal" | Vorapaxar | Placebo |
|---|---|---|
| Von Willebrand Factor | 162 (122 to 193) | 234 (151 to 279) |
P-Selectin is quantified using commercially available "ELISA" assays, individual maxima were compared between both study periods.
| ng/ml | Vorapaxar | Placebo |
|---|---|---|
| P-Selectin | 30.8 (21.6 to 33.9) | 33.1 (22.4 to 37.9) |
interleukin-6 concentrations were measured by commercially available "ELISA" assays, individual maxima were compared between both study periods
| pg/mL | Vorapaxar | Placebo |
|---|---|---|
| Interleukin 6 | 105 (74 to 193) | 180 (72 to 370) |
tumor necrosis factor alpha concentrations were measured using commercially available "ELISA" assays, individual maxima were compared between both study periods
| pg/mL | Vorapaxar | Placebo |
|---|---|---|
| Tumor Necrosis Factor Alpha | 27 (13 to 70) | 75 (22 to 96) |
C-reactive protein levels were measured in the certified central laboratory of the General Hospital, 24h values were compared with each other
| mg/dL | Vorapaxar | Placebo |
|---|---|---|
| C-reactive Protein | 1.53 (1.15 to 2.19) | 2.44 (1.57 to 2.82) |
platelet factor 4 concentrations were quantified by "ELISA", individual maxima were compared between both study periods
| pg/mL | Vorapaxar | Placebo |
|---|---|---|
| Platelet Factor 4 | 53310 (36757 to 73273) | 59803 (39446 to 138624) |
thrombomodulin concentrations were measured by commercially available "ELISA" assays, individual maxima were compared between both study periods
| ng/mL | Vorapaxar | Placebo |
|---|---|---|
| Thrombomodulin | 5.05 (4.46 to 5.77) | 5.29 (4.58 to 5.49) |
Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Vorapaxar | 0/15 (0%) | 0/15 (0%) | 11/15 (73.3%) |
| Placebo | 0/16 (0%) | 0/16 (0%) | 12/16 (75%) |
| Event | Vorapaxar | Placebo |
|---|---|---|
| headacheNervous system disorders | 8/15 | 5/16 |
| ChillsGeneral disorders | 4/15 | 7/16 |
| MyalgiaGeneral disorders | 2/15 | 5/16 |
| malaiseGeneral disorders | 2/15 | 0/16 |
| DizzinessGeneral disorders | 1/15 | 0/16 |
| exanthemaSkin and subcutaneous tissue disorders | 0/15 | 1/16 |
| Age, Categorical(Participants) | Vorapaxar | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 8 | 8 | 16 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Vorapaxar | Placebo | Total |
|---|---|---|---|
| Median | 34 (30 to 36) | 27 (22 to 31) | 31 (27 to 34) |
| Sex: Female, Male(Participants) | Vorapaxar | Placebo | Total |
|---|---|---|---|
| Female | 1 | 0 | 1 |
| Male | 7 | 8 | 15 |
| Race and Ethnicity Not Collected(Participants) | Vorapaxar | Placebo | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(participants) | Vorapaxar | Placebo | Total |
|---|---|---|---|
| Austria | 8 | 8 | 16 |
| weight(kg) | Vorapaxar | Placebo | Total |
|---|---|---|---|
| Median | 70 (64 to 84) | 84 (73 to 88) | 77 (67 to 88) |
Plan to share: 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)
No publications or documents are linked to this record.
Ran from Jun 2016 to primary completion in Nov 2016, 5 months.
Results were first posted in Jan 2020, 3 years 1 month after primary completion.
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This study is completed, as verified in Dec 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Vorapaxar
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