EndotoxemiaNCT02612480
Ticagrelor in Human Endotoxemia Response to Human Endotoxemia
A study testing ticagrelor, Clopidogrel and Acetylsalicylic acid lysinate in people with Endotoxemia, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: In patients suffering a myocardial infarction the P2Y12 receptor antagonists prasugrel and ticagrelor improve outcome and prognosis compared to clopidogrel. Moreover, ticagrelor lowers mortality from pulmonary infections and sepsis, which cannot solely be explained by its platelet-inhibiting effect. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Endotoxemia
- What is being tested?
- ticagrelor, Clopidogrel and Acetylsalicylic acid lysinate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2015to Dec 2015
- Phase
- Interventional
- 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 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age ≥ 18 and ≤ 35 years
- Male
- No known current medical/psychiatric diseases
Who cannot join
- History, signs or symptoms of any cardiovascular disease
- History of chronic obstructive pulmonary disease (COPD) or asthma
- History of hemorrhagic diathesis, or any other disorder associated with increased risk of bleeding
- Previous spontaneous vagal collapse
- Use of any medication
- Smoking
Show all 21Show fewer
- Liver enzyme abnormalities (defined as ALAT and/or ASAT > twice upper limit of normality)
- Thrombocytopenia (<150*109
- /ml) or anemia (haemoglobin < 8.0 mmol/L)
- Any obvious disease associated with immune deficiency
- Febrile illness in the week before the LPS challenge
- Hypersensitivity to ticagrelor or any excipients
- Active pathological bleeding
- History of intracranial haemorrhage
- History of dyspepsia
- quantitative bleeding assessment tool (BAT) score >3 (see Appendix 1)
- Participation in another drug trial or donation of blood 3 months prior, until 3 months after the planned LPS challenge
- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block, third degree atrioventricular block or a complex bundle branch block
- Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
- Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
- Renal impairment (defined as MDRD < 60 ml/min)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Intensive Care Medicine, Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6500HB
About this study
Official title: The Effect of Ticagrelor on the Inflammatory Response to Human Endotoxemia
Rationale:
In patients suffering a myocardial infarction the P2Y12 receptor antagonists prasugrel and ticagrelor improve outcome and prognosis compared to clopidogrel. Moreover, ticagrelor lowers mortality from pulmonary infections and sepsis, which cannot solely be explained by its platelet-inhibiting effect. An effect on the inflammatory response in the setting of acute myocardial might underlie this phenomenon and if substantiated support a novel beneficial mechanism of the new the P2Y12 receptor antagonists.
Read more
Objective:
To study whether ticagrelor, added to acetylsalicylic acid, modulates the inflammatory response to the administration of lipopolysaccharide (LPS) in humans in vivo, and to compare this effect with the P2Y12 antagonist clopidogrel.
Study design:
Prospective randomized placebo-controlled trial, according to a PROBE design (prospective randomized open blinded-endpoint study).
Study population:
Forty healthy male volunteers aged ≥ 18 and ≤ 35 years. Intervention (if applicable): Participants will be randomized to receive either placebo (twice daily), acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg) + placebo (once daily), acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg) + ticagrelor (90 mg twice daily, after a loading dose of 180 mg) or acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg)+ clopidogrel (75 mg once daily, after a loading dose of 300mg).
Main study parameters/endpoints:
Endpoints: area under the curve of the proinflammatory cytokines TNF-alpha, IL6, IL-10, IL1ra IL-8, IL-1β, MCP-1 MIP-1a, MIP-1b en IFN; peak concentrations of the various cytokines; plasma concentration of HMGP1; platelet-monocyte complex formation and markers of platelet function; plasma concentration of adenosine.
- Conditions
- Endotoxemia
- Being tested
- ticagrelor, Clopidogrel, Acetylsalicylic acid lysinate, Placebo
- Keywords
- endotoxin, LPS, ticagrelor, clopidogrel, acetylsalicyclic acid, placebo
- Medical subject headings
- Endotoxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ticagrelorDrug
Also called brillique
7 day treatment of ticagrelor 2dd90mg after a loading dose of 180mg
ClopidogrelDrug
Also called Plavix
7 day treatment of clopidogrel 1d75mg after a loading dose of 300mg
Acetylsalicylic acid lysinateDrug
Also called Aspirin
7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg
PlaceboDrug
7 day treatment with placebo
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor and acetylsalicylic acid | Experimental | 7 day treatment with ticagrelor 2x90mg after a loading dose of 180 mg and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg. Receives: Drug: ticagrelor; Drug: Acetylsalicylic acid lysinate |
| Clopidogrel and acetylsalicylic acid | Active comparator | 7 day treatment with clopidogrel x75 mg after a loading dose of 300 mg and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg Receives: Drug: Clopidogrel; Drug: Acetylsalicylic acid lysinate |
| Placebo and acetylsalicylic acid | Placebo comparator | 7 day treatment with placebo and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg Receives: Drug: Acetylsalicylic acid lysinate; Drug: Placebo |
| Placebo | Placebo comparator | 7 day treatment with 2 placebos Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
concentration plasma TNFalpha (pg/ml)
measured with Luminex assay
Measured: measured after challenge with endotoxin at day 7 of medication
Secondary outcomes (21)
concentration plasma IL-6 (pg/ml)
measured with Luminex assay
Measured: measured after challenge with endotoxin at day 7 of medication
concentration plasma IL-8 (pg/ml)
measured with Luminex assay
Measured: measured after challenge with endotoxin at day 7 of medication
concentration plasma IL-10 (pg/ml)
measured with Luminex assay
Measured: measured after challenge with endotoxin at day 7 of medication
concentration plasma IL-1RA (pg/ml)
measured with Luminex assay
Measured: measured after challenge with endotoxin at day 7 of medication
concentration plasma IL-1beta (pg/ml)
measured with Luminex assay
Measured: measured after challenge with endotoxin at day 7 of medication
concentration plasma MCP-1(pg/ml)
measured with Luminex assay
Measured: measured after challenge with endotoxin at day 7 of medication
concentration plasma MIP-1a(pg/ml)
measured with Luminex assay
Measured: measured after challenge with endotoxin at day 7 of medication
concentration plasma MIP-1b(pg/ml)
Measured: measured after challenge with endotoxin at day 7 of medication
concentration plasma IFNgamma(pg/ml)
measured with Luminex assay
Measured: measured after challenge with endotoxin at day 7 of medication
plasma adenosine
Measured: measured after challenge with endotoxin at day 7 of medication
platelet monocyte complexes
flowcytometric determination of monocytic load with platelets
Measured: measured after challenge with endotoxin at day 7 of medication
platelet neutrophil complexes
flowcytometric determination of neutrophil load with platelets
Measured: measured after challenge with endotoxin at day 7 of medication
platelet reactivity
ex vivo stimulation of platelets with ADP and collagen, response measured as P-selectin and fibrinogen)
Measured: measured after challenge with endotoxin at day 7 of medication
monocytic tissue factor expression
tissue factor expression on monocytes as measured by flow cytometry
Measured: measured after challenge with endotoxin at day 7 of medication
monocytic HLA-DR expression
as measured by flow cytometry
Measured: measured after challenge with endotoxin at day 7 of medication
CD14/16 ratio
measured with flow cytometry
Measured: measured after challenge with endotoxin at day 7 of medication
platelet von Willebrandfactor expression
measured with flow cytometry
Measured: measured after challenge with endotoxin at day 7 of medication
VASP-P
ELISA
Measured: difference between measurement prior to start of study drug after challenge with endotoxin at day 7 of medication
symptoms during endotoxin day
6 point likert scale
Measured: measured after challenge with endotoxin at day 7 of medication
blood pressure
mmHg
Measured: measured after challenge with endotoxin at day 7 of medication
temperature
tympanic temperature
Measured: measured after challenge with endotoxin at day 7 of medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2015 (estimated)
- Study startOct 2015
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EndotoxemiaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Pickkers, Radboud University Medical Center
- Investigators
- Peter Pickkers, MD, PhD, Principal investigator, Radboud University Medical CenterNiels Riksen, MD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02612480
- Sponsor's protocol ID
- tica-lps
- Other IDs
- 2014-005537-30, NL51923.091.14, 2014
- Status last verified
- Dec 2015
- First submitted
- 3 Nov 2015
- Last updated
- 15 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Ticagrelor on the Inflammatory Response to Human Endotoxemia
- ClinicalTrials.gov ID
- NCT02612480
- Acronym / sponsor ID
- tica-lps
- Conditions
- Endotoxemia
- Keywords
- endotoxin, LPS, ticagrelor, clopidogrel, acetylsalicyclic acid, placebo
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 23 Nov 2015 (estimated)
- 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.
Rationale:
In patients suffering a myocardial infarction the P2Y12 receptor antagonists prasugrel and ticagrelor improve outcome and prognosis compared to clopidogrel. Moreover, ticagrelor lowers mortality from pulmonary infections and sepsis, which cannot solely be explained by its platelet-inhibiting effect. An effect on the inflammatory response in the setting of acute myocardial might underlie this phenomenon and if substantiated support a novel beneficial mechanism of the new the P2Y12 receptor antagonists.
Objective:
To study whether ticagrelor, added to acetylsalicylic acid, modulates the inflammatory response to the administration of lipopolysaccharide (LPS) in humans in vivo, and to compare this effect with the P2Y12 antagonist clopidogrel.
Study design:
Prospective randomized placebo-controlled trial, according to a PROBE design (prospective randomized open blinded-endpoint study).
Study population:
Forty healthy male volunteers aged ≥ 18 and ≤ 35 years. Intervention (if applicable): Participants will be randomized to receive either placebo (twice daily), acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg) + placebo (once daily), acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg) + ticagrelor (90 mg twice daily, after a loading dose of 180 mg) or acetylsalicylic acid (80 mg once daily, after a loading dose of 160 mg)+ clopidogrel (75 mg once daily, after a loading dose of 300mg).
Main study parameters/endpoints:
Endpoints: area under the curve of the proinflammatory cytokines TNF-alpha, IL6, IL-10, IL1ra IL-8, IL-1β, MCP-1 MIP-1a, MIP-1b en IFN; peak concentrations of the various cytokines; plasma concentration of HMGP1; platelet-monocyte complex formation and markers of platelet function; plasma concentration of adenosine.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor and acetylsalicylic acid | Experimental | Drug: ticagrelor, Drug: Acetylsalicylic acid lysinate7 day treatment with ticagrelor 2x90mg after a loading dose of 180 mg and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg. |
| Clopidogrel and acetylsalicylic acid | Active comparator | Drug: Clopidogrel, Drug: Acetylsalicylic acid lysinate7 day treatment with clopidogrel x75 mg after a loading dose of 300 mg and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg |
| Placebo and acetylsalicylic acid | Placebo comparator | Drug: Acetylsalicylic acid lysinate, Drug: Placebo7 day treatment with placebo and acetylsalicyclic acid 1x80mg after a loading dose of 160 mg |
| Placebo | Placebo comparator | Drug: Placebo7 day treatment with 2 placebos |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age ≥ 18 and ≤ 35 years
- Male
- No known current medical/psychiatric diseases
Key exclusion criteria (21 listed)
- History, signs or symptoms of any cardiovascular disease
- History of chronic obstructive pulmonary disease (COPD) or asthma
- History of hemorrhagic diathesis, or any other disorder associated with increased risk of bleeding
- Previous spontaneous vagal collapse
- Use of any medication
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 |
|---|---|---|
| ticagrelorAlso: brillique7 day treatment of ticagrelor 2dd90mg after a loading dose of 180mg | Drug | Ticagrelor and acetylsalicylic acid |
| ClopidogrelAlso: Plavix7 day treatment of clopidogrel 1d75mg after a loading dose of 300mg | Drug | Clopidogrel and acetylsalicylic acid |
| Acetylsalicylic acid lysinateAlso: Aspirin7 day treatment of acetylsalicyclic acid 1d80mg after a loading dose of 160mg | Drug | Clopidogrel and acetylsalicylic acid, Placebo and acetylsalicylic acid, Ticagrelor and acetylsalicylic acid |
| Placebo7 day treatment with placebo | Drug | Placebo, Placebo and acetylsalicylic acid |
Primary outcome
concentration plasma TNFalpha (pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
measured with Luminex assay
21 secondary outcomes
concentration plasma IL-6 (pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
concentration plasma IL-8 (pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
concentration plasma IL-10 (pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
concentration plasma IL-1RA (pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
concentration plasma IL-1beta (pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
concentration plasma MCP-1(pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
concentration plasma MIP-1a(pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
concentration plasma MIP-1b(pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
concentration plasma IFNgamma(pg/ml)
Time frame: measured after challenge with endotoxin at day 7 of medication
plasma adenosine
Time frame: measured after challenge with endotoxin at day 7 of medication
platelet monocyte complexes
Time frame: measured after challenge with endotoxin at day 7 of medication
platelet neutrophil complexes
Time frame: measured after challenge with endotoxin at day 7 of medication
platelet reactivity
Time frame: measured after challenge with endotoxin at day 7 of medication
monocytic tissue factor expression
Time frame: measured after challenge with endotoxin at day 7 of medication
monocytic HLA-DR expression
Time frame: measured after challenge with endotoxin at day 7 of medication
CD14/16 ratio
Time frame: measured after challenge with endotoxin at day 7 of medication
platelet von Willebrandfactor expression
Time frame: measured after challenge with endotoxin at day 7 of medication
VASP-P
Time frame: difference between measurement prior to start of study drug after challenge with endotoxin at day 7 of medication
symptoms during endotoxin day
Time frame: measured after challenge with endotoxin at day 7 of medication
blood pressure
Time frame: measured after challenge with endotoxin at day 7 of medication
temperature
Time frame: measured after challenge with endotoxin at day 7 of medication
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2015.
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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.
Peter Pickkers, MD, PhD principal investigator
Radboud University Medical Center
Niels Riksen, MD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ticagrelor, Clopidogrel and Acetylsalicylic acid lysinate in people with Endotoxemia, run by Radboud University Medical Center at 1 site in Netherlands.
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 3 inclusion and 21 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 15 Dec 2015. 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 Netherlands. 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.
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?
concentration plasma TNFalpha (pg/ml) (time frame: measured after challenge with endotoxin at day 7 of medication). 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 15 Dec 2015.