Immune DefectIRBOcompNCT04010396
Immunological Responses in Bovine vs Mechanical Composite Grafts
An observational study of Immune Defect, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
In the first retrospective part of the study the investigators will conduct a data analysis of patients having received a bovine aortic graft. The investigators will analyze charts and CT / MRI at various time intervals and identify if there are signs of inflammation. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Immune Defect
- What is being tested?
- Blood sampling
- How many people
- 30 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Sep 2019to 30 Apr 2020
- Phase
- Observational
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Part 1: n=116 bovine (total amount of recipients of the Shelhigh graft at the investigators' institution). 50 (mechanical control) Part 2: n= 10 (bovine with immune response) +10 (bovine without immune response) +10 (mechanical control)
Who may be able to join
- Recipients of the bovine graft or mechanical graft. For the prospective part 2: able to give informed consent by signature, age, matching characteristics and time frame.
Who cannot join
- Individuals of the patient cohort from the last 20 years who indicated that their data cannot be utilized for future research will be excluded from the study.
- Inability or any contraindications to undergo the planned investigated intervention, clinically significant concomitant diseases precluding ambulatory control in the day clinic in Bern.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical and Immunological Patterns of Non-infectious Aortic Graft Inflammation in Bovine vs Non-biological Grafts
In the first retrospective part of the study the investigators will conduct a data analysis of patients having received a bovine aortic graft. The investigators will analyze charts and CT / MRI at various time intervals and identify if there are signs of inflammation.
In the second prospective part the investigators will select survivors from the first part with and without inflammation signs. If they consent to participate in the study the investigators will do a blood sampling in order to perform further immunological analysis. Additionally, the investigators will examine their quality of life by QoL SF-12 questionnaire.
Read the detailed description
Part 1 Retrospective database search on subjects that received a Shelhigh graft (n= 116) and subjects that received a mechanical graft (n=50) in a similar time frame, age, gender, co-morbidities, clinical history.
Analyzing CT or MRI report at following time intervals: 3 - 6 months postoperatively, 1, 2 and 3 years postoperatively (regular check-up appointments in clinics).
Additionally, extraction of following data-set (based on availability): temperature, lab values (C-reactive protein, white blood count, Eosinophil count), pathology report and CT- / MRI- imaging in cases of re-operation.
Firstly, identify if there is a graft inflammation (positive / negative group within the bovine group).
Secondly, compare to mechanical group.
Part 2 Choose 10 + 10 patients of the bovine group (with / without immune response) and 10 of the mechanical group in order to conduct further immunological testing and comparison. The immunological testing will include measurement of immunoglobulin E and immunoglobulin G antibodies against bovine protein, as well as in vitro T cell reactivity in Interleukin 4 and interferon-gamma Elispot. These parameters will characterize whether the patient mounted an adaptive immune response against the bovine protein. In addition, the investigators will measure total immunoglobulin G4 and Interleukin-6 levels in the serum of all patients, as additional inflammation markers.
Contact patients to come into clinics for a visit, explain study. Blood sampling (1 serum and 1 EDTA) after patients consent.
Material will be sampled and sent in anonymized form via express courier to the Translational Immunology Lab at the University Hospital Basel. Samples will be processed within 24h to isolate peripheral blood mononuclear cells (PBMC) and serum. PBMC and Serum will be cryopreserved at -180°C and -80°C respectively. Samples will be analyzed in batches each including 3-5 subjects per group.
- Conditions
- Immune Defect
- Being tested
- Blood sampling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplingOther
Blood sampling: 1 EDTA and 1 Serum vial
| Study group | Role | What they receive |
|---|---|---|
| Recipients of Bovine Graft | Recruitment and informed consent procedure for blood sampling to conduct immunological testing. In addition a questionnaire on QOL (SF-12) will be used to evaluate the most actual quality of life of these patients. Receives: Other: Blood sampling | |
| Recipients of Mechanical Graft | Recruitment and informed consent procedure for blood sampling to conduct immunological testing. In addition a questionnaire on QOL (SF-12) will be used to evaluate the most actual quality of life of these patients. Receives: Other: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inflammatory Response
Percentage of patients having received the bovine conduit graft showing a graft inflammation.
Measured: postoperatively, up to 30 years
Secondary outcomes (1)
Inflammatory Response in Control Group
Comparison of the bovine group to patients having received a mechanical composite graft.
Measured: postoperatively, up to 30 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2019
- Study start1 Sep 2019
- Primary completion31 Dec 2019
- Study completion30 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Immune DefectStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe 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
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- ThierryThierry Prof. Dr. med. Carrel, Study chair, Department Chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04010396
- Sponsor's protocol ID
- 24.06.2019 V 1.0
- Acronym
- IRBOcomp
- Status last verified
- Nov 2021
- First submitted
- 3 Jul 2019
- Last updated
- 23 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Carrel TP, Schoenhoff FS, Schmidli J, Stalder M, Eckstein FS, Englberger L. Deleterious outcome of No-React-treated stentless valved conduits after aortic root replacement: why were warnings ignored? J Thorac Cardiovasc Surg. 2008 Jul;136(1):52-7. doi: 10.1016/j.jtcvs.2007.09.047. Epub 2008 May 27.
PubMed 18603053Carrel T, Reineke D, Englberger L. Another report on unfavourable long-term outcome following implantation of the Shelhigh No-React valved tube graft. Eur J Cardiothorac Surg. 2016 Dec;50(6):1179-1180. doi: 10.1093/ejcts/ezw205. Epub 2016 Jun 14. No abstract available.
PubMed 27307482Reineke DC, Kaya A, Heinisch PP, Oezdemir B, Winkler B, Huber C, Heijmen RH, Morshuis W, Carrel TP, Englberger L. Long-term follow-up after implantation of the Shelhigh(R) No-React(R) complete biological aortic valved conduit. Eur J Cardiothorac Surg. 2016 Jul;50(1):98-104. doi: 10.1093/ejcts/ezv452. Epub 2015 Dec 30.
PubMed 26719402Gisler F, Huber C, Wenaweser P, Carrel T. Severe calcification of a Shelhigh stentless valved conduit. Eur J Cardiothorac Surg. 2014 Aug;46(2):334. doi: 10.1093/ejcts/ezt569. Epub 2013 Dec 11. No abstract available.
PubMed 24335263Schoenhoff FS, Loup O, Gahl B, Banz Y, Pavlovic M, Pfammatter JP, Carrel TP, Kadner A. The Contegra bovine jugular vein graft versus the Shelhigh pulmonic porcine graft for reconstruction of the right ventricular outflow tract: a comparative study. J Thorac Cardiovasc Surg. 2011 Mar;141(3):654-61. doi: 10.1016/j.jtcvs.2010.06.068. Epub 2011 Jan 20.
PubMed 21255796Carrel TP. Another disastrous outcome following aortic root replacement with the Shelhigh No-react aortic valved tube. Thorac Cardiovasc Surg. 2008 Aug;56(5):314-5. doi: 10.1055/s-2008-1038472. No abstract available.
PubMed 18615385Englberger L, Noti J, Immer FF, Stalder M, Eckstein FS, Carrel TP. The Shelhigh No-React bovine internal mammary artery: a questionable alternative conduit in coronary bypass surgery? Eur J Cardiothorac Surg. 2008 Feb;33(2):222-4. doi: 10.1016/j.ejcts.2007.11.006. Epub 2007 Dec 20.
PubMed 18083039Sahin A, Muggler O, Sromicki J, Caliskan E, Reser D, Emmert MY, Alkadhi H, Maisano F, Falk V, Holubec T. Long-term follow-up after aortic root replacement with the Shelhigh(R) biological valved conduit: a word of caution! Eur J Cardiothorac Surg. 2016 Dec;50(6):1172-1178. doi: 10.1093/ejcts/ezw167. Epub 2016 May 26.
PubMed 27229673Kaya A, Heijmen RH, Kelder JC, Schepens MA, Morshuis WJ. Stentless biological valved conduit for aortic root replacement: initial experience with the Shelhigh BioConduit model NR-2000C. J Thorac Cardiovasc Surg. 2011 May;141(5):1157-62. doi: 10.1016/j.jtcvs.2010.07.009. Epub 2010 Sep 15.
PubMed 20832085
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Immunological Patterns of Non-infectious Aortic Graft Inflammation in Bovine vs Non-biological Grafts
- ClinicalTrials.gov ID
- NCT04010396
- Acronym / sponsor ID
- IRBOcomp / 24.06.2019 V 1.0
- Conditions
- Immune Defect
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 8 Jul 2019 (actual)
- 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.
In the first retrospective part of the study the investigators will conduct a data analysis of patients having received a bovine aortic graft. The investigators will analyze charts and CT / MRI at various time intervals and identify if there are signs of inflammation.
In the second prospective part the investigators will select survivors from the first part with and without inflammation signs. If they consent to participate in the study the investigators will do a blood sampling in order to perform further immunological analysis. Additionally, the investigators will examine their quality of life by QoL SF-12 questionnaire.
Detailed description
Part 1 Retrospective database search on subjects that received a Shelhigh graft (n= 116) and subjects that received a mechanical graft (n=50) in a similar time frame, age, gender, co-morbidities, clinical history.
Analyzing CT or MRI report at following time intervals: 3 - 6 months postoperatively, 1, 2 and 3 years postoperatively (regular check-up appointments in clinics).
Additionally, extraction of following data-set (based on availability): temperature, lab values (C-reactive protein, white blood count, Eosinophil count), pathology report and CT- / MRI- imaging in cases of re-operation.
Firstly, identify if there is a graft inflammation (positive / negative group within the bovine group).
Secondly, compare to mechanical group.
Part 2 Choose 10 + 10 patients of the bovine group (with / without immune response) and 10 of the mechanical group in order to conduct further immunological testing and comparison. The immunological testing will include measurement of immunoglobulin E and immunoglobulin G antibodies against bovine protein, as well as in vitro T cell reactivity in Interleukin 4 and interferon-gamma Elispot. These parameters will characterize whether the patient mounted an adaptive immune response against the bovine protein. In addition, the investigators will measure total immunoglobulin G4 and Interleukin-6 levels in the serum of all patients, as additional inflammation markers.
Contact patients to come into clinics for a visit, explain study. Blood sampling (1 serum and 1 EDTA) after patients consent.
Material will be sampled and sent in anonymized form via express courier to the Translational Immunology Lab at the University Hospital Basel. Samples will be processed within 24h to isolate peripheral blood mononuclear cells (PBMC) and serum. PBMC and Serum will be cryopreserved at -180°C and -80°C respectively. Samples will be analyzed in batches each including 3-5 subjects per group.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Recipients of Bovine Graft | – | Other: Blood samplingRecruitment and informed consent procedure for blood sampling to conduct immunological testing. In addition a questionnaire on QOL (SF-12) will be used to evaluate the most actual quality of life of these patients. |
| Recipients of Mechanical Graft | – | Other: Blood samplingRecruitment and informed consent procedure for blood sampling to conduct immunological testing. In addition a questionnaire on QOL (SF-12) will be used to evaluate the most actual quality of life of these patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Part 1: n=116 bovine (total amount of recipients of the Shelhigh graft at the investigators' institution). 50 (mechanical control) Part 2: n= 10 (bovine with immune response) +10 (bovine without immune response) +10 (mechanical control)
Key inclusion criteria (1 listed)
- Recipients of the bovine graft or mechanical graft. For the prospective part 2: able to give informed consent by signature, age, matching characteristics and time frame.
Key exclusion criteria (2 listed)
- Individuals of the patient cohort from the last 20 years who indicated that their data cannot be utilized for future research will be excluded from the study.
- Inability or any contraindications to undergo the planned investigated intervention, clinically significant concomitant diseases precluding ambulatory control in the day clinic in Bern.
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 |
|---|---|---|
| Blood samplingBlood sampling: 1 EDTA and 1 Serum vial | Other | Recipients of Bovine Graft, Recipients of Mechanical Graft |
Primary outcome
Inflammatory Response
Time frame: postoperatively, up to 30 years
Percentage of patients having received the bovine conduit graft showing a graft inflammation.
1 secondary outcome
Inflammatory Response in Control Group
Time frame: postoperatively, up to 30 years
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 23 Nov 2021.
- Background: PubMed 18603053Carrel TP, Schoenhoff FS, Schmidli J, Stalder M, Eckstein FS, Englberger L. Deleterious outcome of No-React-treated stentless valved conduits after aortic root replacement: why were warnings ignored? J Thorac Cardiovasc Surg. 2008 Jul;136(1):52-7. doi: 10.1016/j.jtcvs.2007.09.047. Epub 2008 May 27.
- Background: PubMed 27307482Carrel T, Reineke D, Englberger L. Another report on unfavourable long-term outcome following implantation of the Shelhigh No-React valved tube graft. Eur J Cardiothorac Surg. 2016 Dec;50(6):1179-1180. doi: 10.1093/ejcts/ezw205. Epub 2016 Jun 14. No abstract available.
- Background: PubMed 26719402Reineke DC, Kaya A, Heinisch PP, Oezdemir B, Winkler B, Huber C, Heijmen RH, Morshuis W, Carrel TP, Englberger L. Long-term follow-up after implantation of the Shelhigh(R) No-React(R) complete biological aortic valved conduit. Eur J Cardiothorac Surg. 2016 Jul;50(1):98-104. doi: 10.1093/ejcts/ezv452. Epub 2015 Dec 30.
- Background: PubMed 24335263Gisler F, Huber C, Wenaweser P, Carrel T. Severe calcification of a Shelhigh stentless valved conduit. Eur J Cardiothorac Surg. 2014 Aug;46(2):334. doi: 10.1093/ejcts/ezt569. Epub 2013 Dec 11. No abstract available.
- Background: PubMed 21255796Schoenhoff FS, Loup O, Gahl B, Banz Y, Pavlovic M, Pfammatter JP, Carrel TP, Kadner A. The Contegra bovine jugular vein graft versus the Shelhigh pulmonic porcine graft for reconstruction of the right ventricular outflow tract: a comparative study. J Thorac Cardiovasc Surg. 2011 Mar;141(3):654-61. doi: 10.1016/j.jtcvs.2010.06.068. Epub 2011 Jan 20.
- Background: PubMed 18615385Carrel TP. Another disastrous outcome following aortic root replacement with the Shelhigh No-react aortic valved tube. Thorac Cardiovasc Surg. 2008 Aug;56(5):314-5. doi: 10.1055/s-2008-1038472. No abstract available.
- Background: PubMed 18083039Englberger L, Noti J, Immer FF, Stalder M, Eckstein FS, Carrel TP. The Shelhigh No-React bovine internal mammary artery: a questionable alternative conduit in coronary bypass surgery? Eur J Cardiothorac Surg. 2008 Feb;33(2):222-4. doi: 10.1016/j.ejcts.2007.11.006. Epub 2007 Dec 20.
- Background: PubMed 27229673Sahin A, Muggler O, Sromicki J, Caliskan E, Reser D, Emmert MY, Alkadhi H, Maisano F, Falk V, Holubec T. Long-term follow-up after aortic root replacement with the Shelhigh(R) biological valved conduit: a word of caution! Eur J Cardiothorac Surg. 2016 Dec;50(6):1172-1178. doi: 10.1093/ejcts/ezw167. Epub 2016 May 26.
- Background: PubMed 20832085Kaya A, Heijmen RH, Kelder JC, Schepens MA, Morshuis WJ. Stentless biological valved conduit for aortic root replacement: initial experience with the Shelhigh BioConduit model NR-2000C. J Thorac Cardiovasc Surg. 2011 May;141(5):1157-62. doi: 10.1016/j.jtcvs.2010.07.009. Epub 2010 Sep 15.
- Individual participant dataSharing planned: No
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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.
ThierryThierry Prof. Dr. med. Carrel study chair
Department Chair
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Immune Defect, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 1 inclusion and 2 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 23 Nov 2021. 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 Switzerland. 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.
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?
Inflammatory Response (time frame: postoperatively, up to 30 years). 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 NCT04010396, which also lists 9 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 23 Nov 2021.