Ischemia-reperfusion InjuryNCT04284592
Remote Ischemic Postconditioning Increases HIF-1α Plasma Levels and Improves Cardiac Markers After Cardiac Surgery
A study testing Remote ischemic post-conditioning (RIP) in people with Ischemia-reperfusion Injury, run by José García de la Asunción.
Trial summary
Background. Cardiopulmonary bypass in on-pump cardiac surgery (OPCS) can have harmful effects by ischemia-reperfusion. No data about the effects of remote ischemic postconditioning (RIP) in hypoxia-inducible factor-1 alpha (HIF-1α) plasma level after OPCS. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ischemia-reperfusion Injury
- What is being tested?
- Remote ischemic post-conditioning (RIP)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- Oct 2012to Oct 2017
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- elective cardiac surgery (coronary arteries and/or valve replacement)
- ASA physical status III or less
Who cannot join
- pregnancy
- previous cardiac surgery
- myocardial infarction (< 6 weeks)
- renal failure
- severe chronic pulmonary disease.
About this study
Official title: Remote Ischemic Postconditioning Increases HIF-1α Plasma Levels and Improves Cardiac Markers After Cardiac Surgery: a Randomised Controlled Study
Background. Cardiopulmonary bypass in on-pump cardiac surgery (OPCS) can have harmful effects by ischemia-reperfusion. No data about the effects of remote ischemic postconditioning (RIP) in hypoxia-inducible factor-1 alpha (HIF-1α) plasma level after OPCS. The aim of this study is evaluate the effects of RIP on postoperative HIF-1α plasma levels, cardiac markers and arterial oxygenation of patients after OPCS.
Methods. Randomised controlled study in 70 patients undergoing OPCS: 35 patients receive RIP (RIP group) and 35 patients not (control group). Patients receive RIP on upper limb: 5 min of ischemia followed by 5 min of reperfusion (3 cycles) immediately after leaving on-pump. The primary outcome was to know the HIF-1α plasma levels after surgery in both groups: before starting surgery (T0) and after CPB period at 2 h (T1), 8 h (T2), 24 h (T3), 36 h (T4), 48 h (T5). Secondary outcomes included to measure the cardiac markers levels (Troponin T, CK-MB, CPK), arterial oxygenation (PaO2/FiO2) and others.
Read the detailed description
Cardiac surgery with cardiopulmonary bypass (CPB) is associated with ischemia-reperfusion (I-R) injury. Acute myocardial injury after cardiac surgery is associated with increased mortality and morbidity. In 1993, reported that brief circumflex artery occlusion reduces myocardial infarct size induced by a definitive occlusion of the left anterior descending artery, a phenomenon which has been named remote ischemic preconditioning (RIPC). This approach confers resistance to subsequent ischemic episodes in remote organs, possibly by transferring protective mediators through humoral, neuronal, and systemic mechanisms, however the mechanisms involved are not yet fully known. A recent study has found that cardioprotection induced by RIPC the mitochondria appear to be an important subcellular effector organelle. It has been reported that RIPC could be a potential protective approach for perioperative complications. Therefore, the effects on myocardial injury and clinical outcome in patients undergoing on-pump cardiac surgery (OPCS) are inconclusive. In the present study, we conducted a randomized clinical trial on patients undergoing OPCS by application of remote ischemic postconditioning (RIP), an alternative to remote ischemic preconditioning. RIP can be applied in different clinical situations, medical or surgical, when reperfusion is initiated and associated to acidosis, nitric oxide formation, mitochondrial permeability transition pore inhibition and reactive oxygen species generation. In the present study we have opted for remote postconditioning because we speculate a possible losses of plasmatic effectors during CPB procedures using polyvinylchloride (PVC) tubing. Since, when blood is exposed to the PVC surface the plasma proteins may be adsorbed. Also to minimize the bleeding or hemodilution effects on the potential protective plasmatic effectors levels during CPB.
Tissue exposure to low O2 concentration starts a hypoxic response of the hypoxia-inducible factor 1 (HIF-1), a transcription factor heterodimer, consisting of an O2 regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit that binds to the consensus sequence 5'-RCGTG-3', which is present near HIF-1-regulated genes. HIF-1α protein stability is upregulated in response to hypoxia. HIF-1α protein stability is negatively regulated by O2-dependent prolyl hydroxylation and is degraded under normoxia by prolyl hydroxylase. HIF-1α plays a critical role in the mammalian cells activating genes associate with angiogenesis, ischemia, energy metabolism and cell cycle.
The aim of this study carried out in patients undergoing OPCS was the determination of the time course of HIF-1α plasma levels in response to RIP and the possible correlation between aortic cross-clamping time and HIF-1α plasma levels in both groups. HIF-1α role in remote ischemic conditioning (pre or post) is very little known. Therefore, we tested the hypothesis that RIP induces cardiac protection after OPCS and that this is associated to an increase of HIF-1α plasma levels.
- Conditions
- Ischemia-reperfusion Injury
- Being tested
- Remote ischemic post-conditioning (RIP)
- Keywords
- on-pump cardiac surgery, HIF-1α, Remote ischemic postconditioning, postoperative cardiac markers, cardiopulmonary bypass
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic post-conditioning (RIP)Procedure or surgery
The limb RIP was applied after leaving of cardiopulmonary bypass and consisted of 3 cycles: 5 min of ischemia by a cuff-inflator on an arm and inflated to 200 mmHg, followed by 5 min deflated. The control group had during the same time a deflated cuff.
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | Patients do not receive remote ischemic post-conditioning (RIP) after cardiopulmonary bypass |
| RIP group | Experimental | Patients receive remote ischemic post-conditioning (RIP) after cardiopulmonary bypass Receives: Procedure: Remote ischemic post-conditioning (RIP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Measured: Before starting surgery, is the basal time (Time 0)
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Measured: 2 hours after cardiopulmonary bypass period (Time 1)
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Measured: 8 hours after cardiopulmonary bypass period (Time 2)
Study of time course of HIF-1α plasma levels (absorbance units) after cardiac surgery
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Measured: 24 hours after cardiopulmonary bypass period (Time 3)
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Measured: 36 hours after cardiopulmonary bypass period (Time 4)
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Measured: 48 hours after cardiopulmonary bypass period (Time 5).
Secondary outcomes (4)
Study of time course of cardiac marker, Troponin T plasma levels (ng/l)
Troponin T (ng/l) plasma levels. Similar to HIF-1α measures were studied in six arterial blood samples, which were collected from a radial artery line at 6 specific time points (Time 0 to Time 5).
Measured: In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).
Study of time course of cardiac marker, creatine phospho-kinase (CPK) plasma levels (U/l)
Creatine phospho-kinase (CPK) plasma levels (U/l). Similar to HIF-1α measures were studied in six arterial blood samples, which were collected from a radial artery line at 6 specific time points (Time 0 to Time 5).
Measured: In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).
Study of time course of cardiac marker, creatine kinase-MB (CK-MB) plasma levels (ng/ml)
Creatine kinase-MB (CK-MB) plasma levels (ng/ml). Similar to HIF-1α measures were studied in six arterial blood samples, which were collected from a radial artery line at 6 specific time points (Time 0 to Time 5).
Measured: In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).
Study of time course of arterial oxygenation marker (PO2/FiO2), after on-pump cardiac surgery
Oxygenation marker (PO2/FiO2). Similar to HIF-1α measures were studied in six arterial blood samples, which were collected from a radial artery line at 6 specific time points (Time 0 to Time 5).
Measured: In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2020
- Study startOct 2012
- Primary completionJun 2015
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Ischemia-reperfusion InjuryStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 35 patients receive RIP on upper limb: 5 min of ischemia followed by 5 min of reperfusion (3 cycles) immediately after leaving on-pump. The primary outcome was to know the time course of HIF-1α plasma levels after surgery in both groups and compare the two groups at specific time points: before starting surgery (T0) and after CPB period at 2 h (T1), 8 h (T2), 24 h (T3), 36 h (T4), 48 h (T5). Secondary outcomes included to measure the cardiac markers levels (Troponin T, CK-MB, CPK), arterial oxygenation (PaO2:FiO2) and others.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- José García de la Asunción
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, José García de la Asunción, Instituto de Investigacion Sanitaria INCLIVA
- Investigators
- José García de la Asunción, MD, PhD, Principal investigator, Instituto de Investigacion Sanitaria INCLIVA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04284592
- Sponsor's protocol ID
- PI07/0836
- Status last verified
- Feb 2020
- First submitted
- 21 Feb 2020
- Last updated
- 26 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993 Mar;87(3):893-9. doi: 10.1161/01.cir.87.3.893.
PubMed 7680290Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D. Remote ischemic conditioning. J Am Coll Cardiol. 2015 Jan 20;65(2):177-95. doi: 10.1016/j.jacc.2014.10.031.
PubMed 25593060Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM; ERICCA Trial Investigators. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. N Engl J Med. 2015 Oct 8;373(15):1408-17. doi: 10.1056/NEJMoa1413534. Epub 2015 Oct 5.
PubMed 26436207Hausenloy DJ, Yellon DM. Ischaemic conditioning and reperfusion injury. Nat Rev Cardiol. 2016 Apr;13(4):193-209. doi: 10.1038/nrcardio.2016.5. Epub 2016 Feb 4.
PubMed 26843289Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4. doi: 10.1073/pnas.92.12.5510.
PubMed 7539918Garcia-de-la-Asuncion J, Pastor E, Perez-Griera J, Belda FJ, Moreno T, Garcia-del-Olmo E, Marti F. Oxidative stress injury after on-pump cardiac surgery: effects of aortic cross clamp time and type of surgery. Redox Rep. 2013;18(5):193-9. doi: 10.1179/1351000213Y.0000000060.
PubMed 24020718Kalakech H, Tamareille S, Pons S, Godin-Ribuot D, Carmeliet P, Furber A, Martin V, Berdeaux A, Ghaleh B, Prunier F. Role of hypoxia inducible factor-1alpha in remote limb ischemic preconditioning. J Mol Cell Cardiol. 2013 Dec;65:98-104. doi: 10.1016/j.yjmcc.2013.10.001. Epub 2013 Oct 17.
PubMed 24140799Cai Z, Luo W, Zhan H, Semenza GL. Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17462-7. doi: 10.1073/pnas.1317158110. Epub 2013 Oct 7.
PubMed 24101519
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remote Ischemic Postconditioning Increases HIF-1α Plasma Levels and Improves Cardiac Markers After Cardiac Surgery: a Randomised Controlled Study
- ClinicalTrials.gov ID
- NCT04284592
- Acronym / sponsor ID
- PI07/0836
- Conditions
- Ischemia-reperfusion Injury
- Keywords
- on-pump cardiac surgery, HIF-1α, Remote ischemic postconditioning, postoperative cardiac markers, cardiopulmonary bypass
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- José García de la AsunciónUniversity, hospital or other
- Study start
- Oct 2012 (actual)
- Primary completion
- Jun 2015 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 26 Feb 2020 (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.
Background. Cardiopulmonary bypass in on-pump cardiac surgery (OPCS) can have harmful effects by ischemia-reperfusion. No data about the effects of remote ischemic postconditioning (RIP) in hypoxia-inducible factor-1 alpha (HIF-1α) plasma level after OPCS. The aim of this study is evaluate the effects of RIP on postoperative HIF-1α plasma levels, cardiac markers and arterial oxygenation of patients after OPCS.
Methods. Randomised controlled study in 70 patients undergoing OPCS: 35 patients receive RIP (RIP group) and 35 patients not (control group). Patients receive RIP on upper limb: 5 min of ischemia followed by 5 min of reperfusion (3 cycles) immediately after leaving on-pump. The primary outcome was to know the HIF-1α plasma levels after surgery in both groups: before starting surgery (T0) and after CPB period at 2 h (T1), 8 h (T2), 24 h (T3), 36 h (T4), 48 h (T5). Secondary outcomes included to measure the cardiac markers levels (Troponin T, CK-MB, CPK), arterial oxygenation (PaO2/FiO2) and others.
Detailed description
Cardiac surgery with cardiopulmonary bypass (CPB) is associated with ischemia-reperfusion (I-R) injury. Acute myocardial injury after cardiac surgery is associated with increased mortality and morbidity. In 1993, reported that brief circumflex artery occlusion reduces myocardial infarct size induced by a definitive occlusion of the left anterior descending artery, a phenomenon which has been named remote ischemic preconditioning (RIPC). This approach confers resistance to subsequent ischemic episodes in remote organs, possibly by transferring protective mediators through humoral, neuronal, and systemic mechanisms, however the mechanisms involved are not yet fully known. A recent study has found that cardioprotection induced by RIPC the mitochondria appear to be an important subcellular effector organelle. It has been reported that RIPC could be a potential protective approach for perioperative complications. Therefore, the effects on myocardial injury and clinical outcome in patients undergoing on-pump cardiac surgery (OPCS) are inconclusive. In the present study, we conducted a randomized clinical trial on patients undergoing OPCS by application of remote ischemic postconditioning (RIP), an alternative to remote ischemic preconditioning. RIP can be applied in different clinical situations, medical or surgical, when reperfusion is initiated and associated to acidosis, nitric oxide formation, mitochondrial permeability transition pore inhibition and reactive oxygen species generation. In the present study we have opted for remote postconditioning because we speculate a possible losses of plasmatic effectors during CPB procedures using polyvinylchloride (PVC) tubing. Since, when blood is exposed to the PVC surface the plasma proteins may be adsorbed. Also to minimize the bleeding or hemodilution effects on the potential protective plasmatic effectors levels during CPB.
Tissue exposure to low O2 concentration starts a hypoxic response of the hypoxia-inducible factor 1 (HIF-1), a transcription factor heterodimer, consisting of an O2 regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit that binds to the consensus sequence 5'-RCGTG-3', which is present near HIF-1-regulated genes. HIF-1α protein stability is upregulated in response to hypoxia. HIF-1α protein stability is negatively regulated by O2-dependent prolyl hydroxylation and is degraded under normoxia by prolyl hydroxylase. HIF-1α plays a critical role in the mammalian cells activating genes associate with angiogenesis, ischemia, energy metabolism and cell cycle.
The aim of this study carried out in patients undergoing OPCS was the determination of the time course of HIF-1α plasma levels in response to RIP and the possible correlation between aortic cross-clamping time and HIF-1α plasma levels in both groups. HIF-1α role in remote ischemic conditioning (pre or post) is very little known. Therefore, we tested the hypothesis that RIP induces cardiac protection after OPCS and that this is associated to an increase of HIF-1α plasma levels.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- 35 patients receive RIP on upper limb: 5 min of ischemia followed by 5 min of reperfusion (3 cycles) immediately after leaving on-pump. The primary outcome was to know the time course of HIF-1α plasma levels after surgery in both groups and compare the two groups at specific time points: before starting surgery (T0) and after CPB period at 2 h (T1), 8 h (T2), 24 h (T3), 36 h (T4), 48 h (T5). Secondary outcomes included to measure the cardiac markers levels (Troponin T, CK-MB, CPK), arterial oxygenation (PaO2:FiO2) and others.
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –Patients do not receive remote ischemic post-conditioning (RIP) after cardiopulmonary bypass |
| RIP group | Experimental | Procedure: Remote ischemic post-conditioning (RIP)Patients receive remote ischemic post-conditioning (RIP) after cardiopulmonary bypass |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- elective cardiac surgery (coronary arteries and/or valve replacement)
- ASA physical status III or less
Key exclusion criteria (5 listed)
- pregnancy
- previous cardiac surgery
- myocardial infarction (< 6 weeks)
- renal failure
- severe chronic pulmonary disease.
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 |
|---|---|---|
| Remote ischemic post-conditioning (RIP)The limb RIP was applied after leaving of cardiopulmonary bypass and consisted of 3 cycles: 5 min of ischemia by a cuff-inflator on an arm and inflated to 200 mmHg, followed by 5 min deflated. The control group had during the same time a deflated cuff. | Procedure or surgery | RIP group |
Primary outcome
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Time frame: Before starting surgery, is the basal time (Time 0)
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Time frame: 2 hours after cardiopulmonary bypass period (Time 1)
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Time frame: 8 hours after cardiopulmonary bypass period (Time 2)
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Study of time course of HIF-1α plasma levels (absorbance units) after cardiac surgery
Time frame: 24 hours after cardiopulmonary bypass period (Time 3)
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Time frame: 36 hours after cardiopulmonary bypass period (Time 4)
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery
Time frame: 48 hours after cardiopulmonary bypass period (Time 5).
Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.
4 secondary outcomes
Study of time course of cardiac marker, Troponin T plasma levels (ng/l)
Time frame: In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).
Study of time course of cardiac marker, creatine phospho-kinase (CPK) plasma levels (U/l)
Time frame: In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).
Study of time course of cardiac marker, creatine kinase-MB (CK-MB) plasma levels (ng/ml)
Time frame: In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).
Study of time course of arterial oxygenation marker (PO2/FiO2), after on-pump cardiac surgery
Time frame: In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).
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 26 Feb 2020.
- Background: PubMed 7680290Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993 Mar;87(3):893-9. doi: 10.1161/01.cir.87.3.893.
- Background: PubMed 25593060Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D. Remote ischemic conditioning. J Am Coll Cardiol. 2015 Jan 20;65(2):177-95. doi: 10.1016/j.jacc.2014.10.031.
- Background: PubMed 26436207Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM; ERICCA Trial Investigators. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. N Engl J Med. 2015 Oct 8;373(15):1408-17. doi: 10.1056/NEJMoa1413534. Epub 2015 Oct 5.
- Background: PubMed 26843289Hausenloy DJ, Yellon DM. Ischaemic conditioning and reperfusion injury. Nat Rev Cardiol. 2016 Apr;13(4):193-209. doi: 10.1038/nrcardio.2016.5. Epub 2016 Feb 4.
- Background: PubMed 7539918Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4. doi: 10.1073/pnas.92.12.5510.
- Background: PubMed 24020718Garcia-de-la-Asuncion J, Pastor E, Perez-Griera J, Belda FJ, Moreno T, Garcia-del-Olmo E, Marti F. Oxidative stress injury after on-pump cardiac surgery: effects of aortic cross clamp time and type of surgery. Redox Rep. 2013;18(5):193-9. doi: 10.1179/1351000213Y.0000000060.
- Background: PubMed 24140799Kalakech H, Tamareille S, Pons S, Godin-Ribuot D, Carmeliet P, Furber A, Martin V, Berdeaux A, Ghaleh B, Prunier F. Role of hypoxia inducible factor-1alpha in remote limb ischemic preconditioning. J Mol Cell Cardiol. 2013 Dec;65:98-104. doi: 10.1016/j.yjmcc.2013.10.001. Epub 2013 Oct 17.
- Background: PubMed 24101519Cai Z, Luo W, Zhan H, Semenza GL. Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17462-7. doi: 10.1073/pnas.1317158110. Epub 2013 Oct 7.
- Individual participant dataSharing planned: No
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Kidney Cancer
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.
José García de la Asunción, MD, PhD principal investigator
Instituto de Investigacion Sanitaria INCLIVA
Questions about this trial
What is this clinical trial studying?
A study testing Remote ischemic post-conditioning (RIP) in people with Ischemia-reperfusion Injury, run by José García de la Asunción.
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 2 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: finished, as of the sponsor's last update on 26 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery (time frame: Before starting surgery, is the basal time (Time 0)). The study lists 6 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 NCT04284592, which also lists 8 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 26 Feb 2020.