InflammationPhase 4NCT00426192
Effects of Hemofiltration and Mannitol Treatment on Cardiopulmonary-Bypass Induced Immunosuppression
A Phase 4 study testing i.v. mannitol and hemofiltration in people with Inflammation, run by University Hospital, Saarland at 1 site in Germany.
Trial summary
After cardiac surgery with cardiopulmonar bypass, the LPS-stimulated cytokine response has been previously shown to be depressed. Therefore, in this trial the hypothesis was tested, whether simple immunomodulting interventions like the i.v. Read more about this study
- Who is it for?
- Ages 35 to 80 years, men only
- Conditions the study is for
- Inflammation
- What is being tested?
- i.v. mannitol and hemofiltration
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 52 participants
- Where
- 1 siteGermany
- Study dates
- Oct 2003to Nov 2004
- 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 35 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male patients
- aged 35-80
- elective CABG surgery
Who cannot join
- previous cardiac surgery
- ejection fraction < 40%
- valvular heart disease
- myocardial infarction during the last 3 months
- evidence of concomitant malignant or immunologic diseases
- antecedent medication with corticosteroids or methylxanthines
- hemoglobin < 12 g/dl
- body mass index > 30
Trial locations and contacts
1 site in 1 country.
Germany1 site
University of Saarland, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy
Homburg/Saar, Saarland, 66421
About this study
Official title: Mechanisms of Endotoxin-Tolerance of Human Monocytes After CABG-Sugery - Effects of Hemofiltration and Mannitol Treatment
After cardiac surgery with cardiopulmonar bypass, the LPS-stimulated cytokine response has been previously shown to be depressed. Therefore, in this trial the hypothesis was tested, whether simple immunomodulting interventions like the i.v. adminstration of mannitol of hemofiltration during cardipulmonary bypass can attenuate this immunosuppressing effect.
Read the detailed description
Background Cardiac surgery using cardiopulmonary bypass (CPB) causes a systemic inflammatory response. In addition to this immune response to CPB, a significant impairment of the responsiveness of peripheral blood mononuclear cells (PBMC) to further immunological stimuli has been observed. The aim of our present study was to evaluate the ability of antioxidant therapy with mannitol or hemofiltration during CPB to modulate the observed immunosuppression after CPB.
Methods With ethics committee approval, 52 patients undergoing elective CABG-surgery were prospectively enrolled and randomized into 3 groups (control, 50 g mannitol iv, hemofiltration during CPB). Blood samples were taken after induction of anesthesia (T1), 20 min after separation from CPB (T2) and 24 h postoperatively (T3). Expression density of the monocytic surface receptor CD14, HLA-DR expression and cytokine release (TNF- and IL10) after LPS-stimulation were evaluated.
Results At T2, the CD14dim cell population was maintained in both intervention groups while in the control group there was a significant decrease of this proinflammatory monocytic phenotype. At T3, all groups developed a significant shift towards the antiinflammatory CD14bright population. No significant differences regarding HLA-DR expression or cytokine release could be demonstrated.
Conclusion This study shows that the suppression of the stimulated immune response after CPB can be alleviated by iv administration of mannitol or hemofiltration. In the light of data showing that this depression of the immune response might affect the postoperative course of patients, these results could lead to an improvement of the management of patients undergoing cardiac surgery with CPB.
- Conditions
- Inflammation
- Being tested
- i.v. mannitol, hemofiltration
- Keywords
- Immunedefense Suppression, Cardiopulmonary Bypass, Mannitol, Hemofiltration, Cytokines, Receptors, Surface CD14
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
i.v. mannitolDrug
hemofiltrationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
LPS-stimulated cytokine release
LPS-stimulated CD14 exppression density
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2007 (estimated)
- Study startOct 2003
- Study completionNov 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for InflammationStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Enrolment
- 52 participants
Sponsor and investigators
- Lead sponsor
- University Hospital, Saarland
- Sponsor type
- University, hospital or other
- Collaborators
- Else Kröner Fresenius Foundation
- Investigators
- Hauke Rensing, MD PhD, Principal investigator, University of Saarland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00426192
- Sponsor's protocol ID
- AN-01
- Status last verified
- Jan 2007
- First submitted
- 3 Jan 2007
- Last updated
- 24 Jan 2007
- Results posted
- No
Publications
Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest. 1997 Sep;112(3):676-92. doi: 10.1378/chest.112.3.676.
PubMed 9315800Grundmann U, Rensing H, Adams HA, Falk S, Wendler O, Ebinger N, Bauer M. Endotoxin desensitization of human mononuclear cells after cardiopulmonary bypass: role of humoral factors. Anesthesiology. 2000 Aug;93(2):359-69. doi: 10.1097/00000542-200008000-00013.
PubMed 10910482Wilhelm W, Grundmann U, Rensing H, Werth M, Langemeyer J, Stracke C, Dhingra D, Bauer M. Monocyte deactivation in severe human sepsis or following cardiopulmonary bypass. Shock. 2002 May;17(5):354-60. doi: 10.1097/00024382-200205000-00002.
PubMed 12022753Kleinschmidt S, Wanner GA, Bussmann D, Kremer JP, Ziegenfuss T, Menger MD, Bauer M. Proinflammatory cytokine gene expression in whole blood from patients undergoing coronary artery bypass surgery and its modulation by pentoxifylline. Shock. 1998 Jan;9(1):12-20. doi: 10.1097/00024382-199801000-00002.
PubMed 9466468Ziegenfuss T, Wanner GA, Grass C, Bauer I, Schuder G, Kleinschmidt S, Menger MD, Bauer M. Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair. Intensive Care Med. 1999 Mar;25(3):279-87. doi: 10.1007/s001340050836.
PubMed 10229162
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Endotoxin-Tolerance of Human Monocytes After CABG-Sugery - Effects of Hemofiltration and Mannitol Treatment
- ClinicalTrials.gov ID
- NCT00426192
- Acronym / sponsor ID
- AN-01
- Conditions
- Inflammation
- Keywords
- Immunedefense Suppression, Cardiopulmonary Bypass, Mannitol, Hemofiltration, Cytokines, Receptors, Surface CD14
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants
- Lead sponsor
- University Hospital, SaarlandUniversity, hospital or other
- Collaborators
- Else Kröner Fresenius Foundation
- Study start
- Oct 2003
- Study completion
- Nov 2004
- First posted
- 24 Jan 2007 (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.
After cardiac surgery with cardiopulmonar bypass, the LPS-stimulated cytokine response has been previously shown to be depressed. Therefore, in this trial the hypothesis was tested, whether simple immunomodulting interventions like the i.v. adminstration of mannitol of hemofiltration during cardipulmonary bypass can attenuate this immunosuppressing effect.
Detailed description
Background Cardiac surgery using cardiopulmonary bypass (CPB) causes a systemic inflammatory response. In addition to this immune response to CPB, a significant impairment of the responsiveness of peripheral blood mononuclear cells (PBMC) to further immunological stimuli has been observed. The aim of our present study was to evaluate the ability of antioxidant therapy with mannitol or hemofiltration during CPB to modulate the observed immunosuppression after CPB.
Methods With ethics committee approval, 52 patients undergoing elective CABG-surgery were prospectively enrolled and randomized into 3 groups (control, 50 g mannitol iv, hemofiltration during CPB). Blood samples were taken after induction of anesthesia (T1), 20 min after separation from CPB (T2) and 24 h postoperatively (T3). Expression density of the monocytic surface receptor CD14, HLA-DR expression and cytokine release (TNF- and IL10) after LPS-stimulation were evaluated.
Results At T2, the CD14dim cell population was maintained in both intervention groups while in the control group there was a significant decrease of this proinflammatory monocytic phenotype. At T3, all groups developed a significant shift towards the antiinflammatory CD14bright population. No significant differences regarding HLA-DR expression or cytokine release could be demonstrated.
Conclusion This study shows that the suppression of the stimulated immune response after CPB can be alleviated by iv administration of mannitol or hemofiltration. In the light of data showing that this depression of the immune response might affect the postoperative course of patients, these results could lead to an improvement of the management of patients undergoing cardiac surgery with CPB.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
Who may qualify
- Ages
- 35 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- male patients
- aged 35-80
- elective CABG surgery
Key exclusion criteria (8 listed)
- previous cardiac surgery
- ejection fraction < 40%
- valvular heart disease
- myocardial infarction during the last 3 months
- evidence of concomitant malignant or immunologic diseases
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 |
|---|---|---|
| i.v. mannitol | Drug | – |
| hemofiltration | Procedure or surgery | – |
Primary outcome
LPS-stimulated cytokine release
LPS-stimulated CD14 exppression density
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2007.
- Background: PubMed 9315800Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest. 1997 Sep;112(3):676-92. doi: 10.1378/chest.112.3.676.
- Background: PubMed 10910482Grundmann U, Rensing H, Adams HA, Falk S, Wendler O, Ebinger N, Bauer M. Endotoxin desensitization of human mononuclear cells after cardiopulmonary bypass: role of humoral factors. Anesthesiology. 2000 Aug;93(2):359-69. doi: 10.1097/00000542-200008000-00013.
- Background: PubMed 12022753Wilhelm W, Grundmann U, Rensing H, Werth M, Langemeyer J, Stracke C, Dhingra D, Bauer M. Monocyte deactivation in severe human sepsis or following cardiopulmonary bypass. Shock. 2002 May;17(5):354-60. doi: 10.1097/00024382-200205000-00002.
- Background: PubMed 9466468Kleinschmidt S, Wanner GA, Bussmann D, Kremer JP, Ziegenfuss T, Menger MD, Bauer M. Proinflammatory cytokine gene expression in whole blood from patients undergoing coronary artery bypass surgery and its modulation by pentoxifylline. Shock. 1998 Jan;9(1):12-20. doi: 10.1097/00024382-199801000-00002.
- Background: PubMed 10229162Ziegenfuss T, Wanner GA, Grass C, Bauer I, Schuder G, Kleinschmidt S, Menger MD, Bauer M. Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair. Intensive Care Med. 1999 Mar;25(3):279-87. doi: 10.1007/s001340050836.
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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.
Hauke Rensing, MD PhD principal investigator
University of Saarland
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 i.v. mannitol and hemofiltration in people with Inflammation, run by University Hospital, Saarland at 1 site in Germany.
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 8 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: status not confirmed, as of the sponsor's last update on 24 Jan 2007. 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 Germany. 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. 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?
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?
LPS-stimulated cytokine release. The study lists 2 primary outcomes in all. 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 NCT00426192, which also lists 5 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 24 Jan 2007.