TraumaPhase 3CAESARNCT01275976
Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture
A Phase 3 study testing C1-esterase inhibitor and Saline 0.9% in people with Trauma and Inflammation, run by UMC Utrecht at 1 site in Netherlands.
Trial summary
Trauma and major operation are associated with an excessive inflammation reaction due to tissue injury. This overwhelming immune response is considered to be a major risk factor in the pathogenesis of late inflammatory complications such as acute respiratory distress syndrome (ARDS), multiple organ dysfunction… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Trauma, Inflammation, Sepsis
- What is being tested?
- C1-esterase inhibitor and Saline 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2012to Feb 2015
- Phase
- Phase 3
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Multi trauma patients
- Femur or pelvic fracture
- Injury Severity Score (ISS) ≥ 18
- Age 18-80 yrs
Who cannot join
- Congenital C1-inhibitor deficiency
- Use of immune suppressants
- Pregnancy
- Known hypersensitivity for blood products
- Fixation of femur fracture with external fixation or osteosynthesis
Trial locations and contacts
1 site in 1 country.
About this study
Trauma and major operation are associated with an excessive inflammation reaction due to tissue injury. This overwhelming immune response is considered to be a major risk factor in the pathogenesis of late inflammatory complications such as acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS) and sepsis.
The investigators hypothesize that administration of C1-esterase inhibitor (C1-INH) will attenuate the humane inflammatory response and, thereby, reduce the risk of inflammatory complications due to surgical interventions in trauma patients with a femur or pelvic fracture
Read the detailed description
Systemic inflammation in response to a femur or pelvic fracture and fixation is associated with complications, such as acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). The injury itself, but also the additional fixation procedure give a release of pro-inflammatory cytokines, in particular interleukin (IL)-6. This results in an aggravation of the initial systemic inflammatory response, and will cause in some patients an increased risk on the development of inflammatory complications, like ARDS and MODS. Which can lead to higher morbidity, mortality and prolonged hospital stay.
Various strategies, such as damage control orthopedics, have been proposed to prevent these complications. Another strategy is to decrease the inflammatory reaction caused by the surgical procedure, and by interventions focused on inhibition of the innate inflammatory response. This will lower the risk of complications.
A promising candidate is the endogenously produced serum protein C1-esterase inhibitor (C1-INH). This protein is an acute phase protein, produced by the liver in response to inflammatory conditions. C1-INH is a major inactivator of the complement system, but important additional anti-inflammatory properties have been demonstrated. A previous study of from our laboratory showed that administration of the drug C1-INH significantly reduced the concentration of circulating pro-inflammatory cytokines such as IL-6, during human experimental endotoxemia. Treatment with C1-INH has been proven to be safe in treatment with humans, even in high dosages and in pregnant patients with C1-INH deficiency.
- Conditions
- Trauma, Inflammation, Sepsis, Multiple Organ Dysfunction Syndrome
- Being tested
- C1-esterase inhibitor, Saline 0.9%
- Keywords
- C1-esterase inhibitor, Systemic inflammation, Sepsis, Trauma, Multiple Organ Dysfunction Syndrome, Cytokines
- Medical subject headings
- Wounds and Injuries, Inflammation, Sepsis, Multiple Organ Failure, Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1-esterase inhibitorDrug
Also called Cetor® (RVG 19303)
C1-esterase inhibitor 200 U/kg infusion over 30 minutes, just before the start of the femur or pelvic fixation operation.
Saline 0.9%Other
Infusion, just before the start of the femur or pelvic fixation operation
| Study group | Role | What they receive |
|---|---|---|
| C1-esterase inhibitor | Active comparator | C1-esterase inhibitor, 100 U/kg bodyweight Receives: Drug: C1-esterase inhibitor |
| Saline 0.9% | Placebo comparator | Saline 0.9% Receives: Other: Saline 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delta Interleukine-6
Measured: 6 hours after C1-INH administration
Secondary outcomes (4)
Cytokines and other markers of inflammation
Measured: up to 12 days after C1-INH administration
Neutrophil redistribution and phenotype
Measured: Up to 12 days after C1-INH administration
C1-inhibitor and complement concentration and activity
Measured: Up to 12 days after C1-INH administration
Hemodynamic response
Measured: Up to 12 days after C1-INH administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2011 (estimated)
- Study startApr 2012
- Primary completionFeb 2015
- Study completionFeb 2015
Why it stopped: Futility and limited feasibility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TraumaStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Prothya Biosolutions
- Responsible party
- Principal investigator, Prof. dr Leenen, UMC Utrecht
- Investigators
- Luke P Leenen, MD, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01275976
- Sponsor's protocol ID
- 34932
- Acronym
- CAESAR
- Status last verified
- Feb 2015
- First submitted
- 12 Jan 2011
- Last updated
- 4 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Heeres M, Visser T, van Wessem KJ, Koenderman AH, Strengers PF, Koenderman L, Leenen LP. The effect of C1-esterase inhibitor on systemic inflammation in trauma patients with a femur fracture - The CAESAR study: study protocol for a randomized controlled trial. Trials. 2011 Oct 11;12:223. doi: 10.1186/1745-6215-12-223.
PubMed 21988742
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture
- ClinicalTrials.gov ID
- NCT01275976
- Acronym / sponsor ID
- CAESAR / 34932
- Conditions
- Trauma, Inflammation, Sepsis, Multiple Organ Dysfunction Syndrome
- Keywords
- C1-esterase inhibitor, Systemic inflammation, Sepsis, Trauma, Multiple Organ Dysfunction Syndrome, Cytokines
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility and limited feasibility
- Enrolment
- 11 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Prothya Biosolutions
- Study start
- Apr 2012
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 13 Jan 2011 (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.
Trauma and major operation are associated with an excessive inflammation reaction due to tissue injury. This overwhelming immune response is considered to be a major risk factor in the pathogenesis of late inflammatory complications such as acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS) and sepsis.
The investigators hypothesize that administration of C1-esterase inhibitor (C1-INH) will attenuate the humane inflammatory response and, thereby, reduce the risk of inflammatory complications due to surgical interventions in trauma patients with a femur or pelvic fracture
Detailed description
Systemic inflammation in response to a femur or pelvic fracture and fixation is associated with complications, such as acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). The injury itself, but also the additional fixation procedure give a release of pro-inflammatory cytokines, in particular interleukin (IL)-6. This results in an aggravation of the initial systemic inflammatory response, and will cause in some patients an increased risk on the development of inflammatory complications, like ARDS and MODS. Which can lead to higher morbidity, mortality and prolonged hospital stay.
Various strategies, such as damage control orthopedics, have been proposed to prevent these complications. Another strategy is to decrease the inflammatory reaction caused by the surgical procedure, and by interventions focused on inhibition of the innate inflammatory response. This will lower the risk of complications.
A promising candidate is the endogenously produced serum protein C1-esterase inhibitor (C1-INH). This protein is an acute phase protein, produced by the liver in response to inflammatory conditions. C1-INH is a major inactivator of the complement system, but important additional anti-inflammatory properties have been demonstrated. A previous study of from our laboratory showed that administration of the drug C1-INH significantly reduced the concentration of circulating pro-inflammatory cytokines such as IL-6, during human experimental endotoxemia. Treatment with C1-INH has been proven to be safe in treatment with humans, even in high dosages and in pregnant patients with C1-INH deficiency.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| C1-esterase inhibitor | Active comparator | Drug: C1-esterase inhibitorC1-esterase inhibitor, 100 U/kg bodyweight |
| Saline 0.9% | Placebo comparator | Other: Saline 0.9%Saline 0.9% |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Multi trauma patients
- Femur or pelvic fracture
- Injury Severity Score (ISS) ≥ 18
- Age 18-80 yrs
Key exclusion criteria (5 listed)
- Congenital C1-inhibitor deficiency
- Use of immune suppressants
- Pregnancy
- Known hypersensitivity for blood products
- Fixation of femur fracture with external fixation or osteosynthesis
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 |
|---|---|---|
| C1-esterase inhibitorAlso: Cetor® (RVG 19303)C1-esterase inhibitor 200 U/kg infusion over 30 minutes, just before the start of the femur or pelvic fixation operation. | Drug | C1-esterase inhibitor |
| Saline 0.9%Infusion, just before the start of the femur or pelvic fixation operation | Other | Saline 0.9% |
Primary outcome
Delta Interleukine-6
Time frame: 6 hours after C1-INH administration
4 secondary outcomes
Cytokines and other markers of inflammation
Time frame: up to 12 days after C1-INH administration
Neutrophil redistribution and phenotype
Time frame: Up to 12 days after C1-INH administration
C1-inhibitor and complement concentration and activity
Time frame: Up to 12 days after C1-INH administration
Hemodynamic response
Time frame: Up to 12 days after C1-INH administration
Results and safety
The study was stopped early (reason given: Futility and limited feasibility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2015.
- Derived from this study: PubMed 21988742Heeres M, Visser T, van Wessem KJ, Koenderman AH, Strengers PF, Koenderman L, Leenen LP. The effect of C1-esterase inhibitor on systemic inflammation in trauma patients with a femur fracture - The CAESAR study: study protocol for a randomized controlled trial. Trials. 2011 Oct 11;12:223. doi: 10.1186/1745-6215-12-223.
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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.
Luke P Leenen, MD, PhD principal investigator
UMC Utrecht
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing C1-esterase inhibitor and Saline 0.9% in people with Trauma and Inflammation, run by UMC Utrecht 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 4 inclusion and 5 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 4 Feb 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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: Futility and limited feasibility). 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?
Delta Interleukine-6 (time frame: 6 hours after C1-INH administration). 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 NCT01275976, which also lists 1 linked publication.
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 4 Feb 2015.