Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Remote Ischemic Preconditioning of Human Myocardium

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01994707
Recruitment Status : Completed
First Posted : November 26, 2013
Last Update Posted : January 12, 2018
Sponsor:
Collaborator:
National Science Centre, Poland
Information provided by (Responsible Party):
Marek Deja, Medical University of Silesia

Brief Summary:

The investigators aim to definitively show if human myocardium can be remotely preconditioned. In the writings there are no experiments that would prove that the remote preconditioning protocol effects on the higher protection of the human myocardial cells, against the ischemia-reperfusion injury.

120 patients referred for coronary artery bypass grafting (CABG) procedure with use of cardiopulmonary bypass are planned will be included to the research. Patients will be randomized (1:1) to one of two groups: remote preconditioning or "placebo" intervention. On the day of surgery, after induction of anesthesia remote preconditioning will be elicited by 3 cycles of 5min inflation (ischemia) and 5 min deflation (reperfusion) of blood pressure cuff on the right arm. In the control group the blood pressure cuff is going to be placed on the upper limb but the preconditioning protocol will not be carried out. On cannulation for CPB, right atrial appendage and myocardial biopsies of the left ventricular will be harvested. The investigators will study: (1) resistance of myocardium to hypoxia/reperfusion injury in in vitro experiments, assessed in isolated right atrial pectinate muscle trabeculae (2) induction of apoptosis and status of mitochondria in myocardium after the period of ischemia, and reperfusion in vitro (3) amount of myocardial necrosis in-vivo induced by period of ischemia and reperfusion during CABG as assessed by postoperative myocardial necrosis markers release (4) the systolic function of the myocardium at the postoperative and the kidney function in the postoperative period evaluated by the creatinine clearance; (5) induction of apoptosis and status of mitochondria in myocardium after the period of ischemia, and reperfusion during coronary artery bypass grafting, assessed in myocardial.

There is going to be an ability to define does the remote preconditioning influence on the occurrence of apoptosis in the human myocardium in the in vivo conditions and does it influence on the postoperative course in patients undergoing cardiac surgery procedures. The investigators will try to study if remote preconditioning modify induction of apoptosis and its structure in response to injury. In case the effect of remote preconditioning is not measurable in ex-vivo assessment, the future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the effect can be confirmed in controlled experimental setting.


Condition or disease Intervention/treatment Phase
Coronary Artery Bypass Graft Triple Vessel Apoptotic DNA Damage Procedure: Remote ischemic preconditioning Procedure: Placebo Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Remote Ischemic Preconditioning of Human Myocardium
Study Start Date : August 2013
Actual Primary Completion Date : January 10, 2016
Actual Study Completion Date : April 27, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Remote ischemic preconditioning
Left arm blood pressure cuff inflation for 5 min then deflation of cuff for 5 min- cycle repeated 3 times before coronary artery bypass grafting.
Procedure: Remote ischemic preconditioning
Blood pressure cuff inflation

Placebo Comparator: Placebo
Deflated cuff on arm for 30 minutes.
Procedure: Placebo
Deflated cuff on arm for 30 minutes.




Primary Outcome Measures :
  1. Troponin-T [ Time Frame: 72 hours ]
    Troponin-T release over the perioperative 72-hour period and its area under the curve (AUC)


Secondary Outcome Measures :
  1. Creatine Kinase isoenzyme MB, full hemodynamic assessment with oxygen metabolic assessment and creatinine clearance (CKD-Epi method) [ Time Frame: 1 week post surgery ]
  2. Resistance of isolated right atrial pectinate muscle trabeculae to simulated hypoxia/reperfusion in functional organ bath model. [ Time Frame: Day 1 of the RICP intervention ]
    All measurements, and in particular recovery of function will be compared between trabeculae from remotely preconditioned and "placebo" patients.

  3. Resistance of isolated right atrial pectinate muscle trabeculae to induction of apoptosis by simulated hypoxia/reperfusion. [ Time Frame: 1day at the moment of harvesting ]

    Two atrial trabeculae from the same appendage, one harvested at baseline, and another subjected to functional experiment (60 min hypoxia + 120 min reoxygenation) studied for:

    • apoptosis induction (Caspase 3 and cleaved Caspase 3, PARP and cleaved PARP -Western-Blot) or
    • apoptosis induction (Caspase 3, cleaved Caspase 3, PARP, cleaved PARP immunohistochemistry, TUNEL) or
    • state of mitochondria (electron microscopy)

  4. Induction of apoptosis and status of mitochondria after the period of ischemia, and reperfusion during coronary artery bypass grafting as assessed in left ventricular myocardial biopsies. [ Time Frame: 1 day at the moment of harvesting ]

    LV myocardium studied for:

    • apoptosis induction (Caspase 3 and cleaved Caspase 3, PARP and cleaved PARP -Western-Blot) or
    • apoptosis induction (Caspase 3, cleaved Caspase 3, PARP, cleaved PARP immunohistochemistry, TUNEL) or
    • state of mitochondria (electron microscopy)

  5. Alveolar-arterial gradient (A-a gradient), S100 concentration, NGAL and zonulin concentration [ Time Frame: 1st week post surgery ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients of both genders.
  2. Patients with stable coronary artery disease referred for surgical revascularization in who at least 3 coronary artery bypass grafts are planned with use of cardiopulmonary bypass.

Exclusion Criteria:

  1. Age below 18 and above 80.
  2. Plan to use radial artery as a graft.
  3. Plan to perform other concomitant cardiac procedure in addition to CABG.
  4. Diabetes mellitus.
  5. Troponin T level before surgery in excess of 99th percentile of upper reference limit.
  6. Acute coronary syndrome in last 14 days before surgery.
  7. Angina pectoris in last 48 hours before surgery.
  8. Significant peripheral vascular disease.
  9. Renal disease with either creatinine level ≥ 2mg/dl or estimated glomerular filtration rate < 30ml/h/1.73m2.
  10. Renal replacement therapy.
  11. Clinically relevant hepatic insufficiency with bilirubin level at least 1.5 times above upper limit of normal or AlAT, AST levels at least 2 times above upper limit of normal.
  12. Advanced lung disease with FEV1 < 40% of predicted value.
  13. Severe systolic dysfunction of left ventricle (EF<35%).
  14. Pregnancy.
  15. Psychiatric disease.
  16. Drug or alcohol abuse.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01994707


Locations
Layout table for location information
Poland
Medical University of Silesia
Katowice, Poland
Sponsors and Collaborators
Medical University of Silesia
National Science Centre, Poland
Investigators
Layout table for investigator information
Principal Investigator: Marek A. Deja, MD PhD Medical University of Silesia
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Marek Deja, MD PhD, Medical University of Silesia
ClinicalTrials.gov Identifier: NCT01994707    
Other Study ID Numbers: NCN-2012/07/B/NZ5/02549
First Posted: November 26, 2013    Key Record Dates
Last Update Posted: January 12, 2018
Last Verified: January 2018
Keywords provided by Marek Deja, Medical University of Silesia:
Remote ischemic preconditioning
Coronary artery bypass graft surgery
Troponin T
Apoptosis
Experimental
Cardioprotection
Additional relevant MeSH terms:
Layout table for MeSH terms
Ischemia
Pathologic Processes