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Healthy VolunteersPhase 4NCT01099566

The Role of the P2Y12 Receptor in Tissue Factor Induced Coagulation

A Phase 4 study testing Prasugrel in people with Healthy Volunteers and Sepsis, run by Medical University of Vienna at 1 site in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Severe sepsis still carries a high mortality rate despite advantages in intensive care medicine and antimicrobial therapy. The inflammatory and procoagulant host response to infection are intricately linked and interactions between platelets, leukocytes and the endothelium play a central role in the pathogenesis of… Read more about this study

Who is it for?
Ages 19 to 40 years, men onlyHealthy volunteers can take part
Conditions the study is for
Healthy Volunteers, Sepsis
What is being tested?
Prasugrel
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteAustria
Study dates
Nov 2009to Nov 2010
Phase
Phase 4
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 19 to 40 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Signed informed consent obtained before any trial-related activities.
  • Men aged >18 and <41 years
  • Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
  • Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant

Who cannot join

  • Known or suspected allergy to trial product or related products (Prasugrel, Clopidogrel, Ticlopidine)
  • Known or suspected hereditary problems of galactose intolerance, Lapp lactase deficiency or glucosegalactose malabsorption
  • Treatment with an investigational drug within three weeks prior to this trial
  • Treatment with a drug (e.g. ketoconazole, omeprazole) that interferes with cytochrome P450, the enzyme responsible for the conversion of prasugrel to its active form, three weeks prior to this trial
  • Participation in an LPS trial within the last 6 weeks
  • Smoking of more than 5 cigarettes per day
Show all 18Show fewer
  • Hereditary deficiency of protein C or S, or a mutation of FV (Leiden), or any other known abnormality affecting coagulation, fibrinolysis or platelet function
  • History of gastro-duodenal ulcera, cardiovascular disease, vasculitis, diabetes mellitus, or hypertension
  • History of brain tumor or history of neurosurgery
  • Hemorrhagic diathesis, trauma or surgery within last 3 months
  • History of hemorrhagic retinopathy
  • Hematuria or detection of occult blood in stool sample
  • Liver or kidney dysfunction
  • Regular use of medication or abuse of alcohol
  • Use of any medication within one week prior to the first trial day
  • Symptoms of a clinically relevant illness in the 3 weeks before the first trial day
  • Excessive sporting activities
  • Weight >95kg and <60kg

Trial locations and contacts

1 site in 1 country.

Austria1 site

  • Medical University of Vienna, Department of Clinical Pharmacology

    Vienna, State of Vienna, A-1090

Other trials in Austria

About this study

Severe sepsis still carries a high mortality rate despite advantages in intensive care medicine and antimicrobial therapy. The inflammatory and procoagulant host response to infection are intricately linked and interactions between platelets, leukocytes and the endothelium play a central role in the pathogenesis of septic shock and disseminated intravascular coagulation (DIC). Interestingly, one key player cell in coagulation, i.e. the platelet, has been somewhat neglected as to its position in the pathogenesis of coagulation abnormalities in sepsis. However, thienopyridines, irreversible platelet P2Y12 ADP-receptor antagonists, e.g. prasugrel, could potentially provide beneficial anticoagulatory and antiinflammatory effects: P2Y12 ADP-receptor antagonists reduce TF-induced coagulation activation in various ex vivo and in vitro models. Moreover, various lines of evidence indicate that thienopyridines may block platelet leukocyte interactions and thereby reduce the propagation of the coagulation and inflammation process.

LPS-infusion in healthy volunteers provides a standardized model to safely study non overt DIC and to document possible effects of therapeutic and prophylactic interventions.

The investigators hypothesize that thienopyridines, irreversible platelet P2Y12 ADP-receptor antagonists, may blunt TF-triggered coagulation activation in humans, which will be studied in a TF-dependent coagulation model in humans.

Being tested
Prasugrel, Placebo
Keywords
human endotoxemia, tissue factor induced coagulation, platelet activation, thienopyridines
Medical subject headings
Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PrasugrelDrug

    Also called Generic name: Prasugrel, Brand name: Efient, Manufacturer: Eli Lilly, Dose: 60mg loading dose (6 tablets a 10mg) on trial day 1

    Prasugrel will be given as loading dose (60mg) on the first trial day two hours prior to endotoxin infusion. Prasugrel is an orally administered prodrug that is converted in the liver by CYP to its active metabolite.

  • PlaceboDrug

    Also called Content: Pills consisting of lactose-starch, Manufacturer: AKH Anstaltsapotheke, Dose: Same number of pills as in the prasugrel period (6 tablets on trial day 1); identically encapsulated by a pharmacist not otherwise involved in the trial

    A pharmacist not otherwise involved in the trial will encapsulate pills consisting of lactose-starch. Six pills will be administered as placebo 2 hours before LPS administration on trial day 1.

Study groups in NCT01099566
Study groupRoleWhat they receive
PrasugrelExperimentalNot described
Receives: Drug: Prasugrel
pills consisting of lactose-starchPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. prothrombin fragments (F1+2)

    To explore whether P2Y12 ADP-receptor antagonism can block activation of the coagulation cascade induced by endotoxemia, in particular decrease LPS mediated thrombin formation as measured by prothrombin fragment (F1+2).

    Measured: -2 to 24 hours after LPS infusion

Secondary outcomes (3)

  1. platelet-leukocyte co-aggregation

    to explore whether P2Y12 ADP-receptor antagonism decreases platelet -leukocyte co-aggregation

    Measured: -2 to 24 hours after LPS infusion

  2. tissue factor expression

    to investigate the influence of P2Y12 ADP-receptor antagonism on tissue factor expression

    Measured: -2 to 24 hours after LPS infusion

  3. anti-platelet effects of prasugrel

    to explore if low dose endotoxemia interferes with the anti-platelet effects of prasugrel

    Measured: -2 to 24 hours after LPS infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2010 (estimated)
  2. Study startNov 2009
  3. Primary completionOct 2010
  4. Study completionNov 2010

Resources

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
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01099566
Sponsor's protocol ID
LPSP2Y12
Other IDs
2008-001320-32, 2008
Status last verified
Jul 2011
First submitted
6 Apr 2010
Last updated
11 Jul 2011
Results posted
No
Data monitoring committee
No

Publications

  • Jilma B, Blann A, Pernerstorfer T, Stohlawetz P, Eichler HG, Vondrovec B, Amiral J, Richter V, Wagner OF. Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin. Am J Respir Crit Care Med. 1999 Mar;159(3):857-63. doi: 10.1164/ajrccm.159.3.9805087.

    PubMed 10051263

  • Pernerstorfer T, Hollenstein U, Hansen JB, Stohlawetz P, Eichler HG, Handler S, Speiser W, Jilma B. Lepirudin blunts endotoxin-induced coagulation activation. Blood. 2000 Mar 1;95(5):1729-34.

    PubMed 10688831

  • Mavrommatis AC, Theodoridis T, Orfanidou A, Roussos C, Christopoulou-Kokkinou V, Zakynthinos S. Coagulation system and platelets are fully activated in uncomplicated sepsis. Crit Care Med. 2000 Feb;28(2):451-7. doi: 10.1097/00003246-200002000-00027.

    PubMed 10708182

  • Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4.

    PubMed 17982182

  • Kirschenbaum LA, Aziz M, Astiz ME, Saha DC, Rackow EC. Influence of rheologic changes and platelet-neutrophil interactions on cell filtration in sepsis. Am J Respir Crit Care Med. 2000 May;161(5):1602-7. doi: 10.1164/ajrccm.161.5.9902105.

    PubMed 10806162

  • Spiel AO, Derhaschnig U, Schwameis M, Bartko J, Siller-Matula JM, Jilma B. Effects of prasugrel on platelet inhibition during systemic endotoxaemia: a randomized controlled trial. Clin Sci (Lond). 2012 Nov;123(10):591-600. doi: 10.1042/CS20120194.

    PubMed 22646240

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Prasugrel in people with Healthy Volunteers and Sepsis, 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 4 inclusion and 18 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 11 Jul 2011. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

prothrombin fragments (F1+2) (time frame: -2 to 24 hours after LPS infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01099566, which also lists 6 linked publications.

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 Jul 2011.

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