Transfusion Related Complication Clinical Trial
Official title:
Phase 1 Study of S-Nitrosylation Therapy to Improve Tissue Oxygenation During Autologous Blood Transfusion in Healthy Volunteer
The Purpose of the study is to test the hypothesis that administration of an S-nitrosylating (SNO) agent can improve tissue oxygenation during transfusion of packed red blood cells (RBCs).
Status | Recruiting |
Enrollment | 20 |
Est. completion date | July 1, 2025 |
Est. primary completion date | July 1, 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 35 Years |
Eligibility | Eligibility Criteria Recruiting and studying of healthy human subjects with no pre-existing pathologic conditions from the local population. As a result the inclusion criteria is deliberately broad. Inclusion Criteria 1. Hemoglobin > 12 g/dl 2. Healthy, non-pregnant adults with no pre-existing blood disorders or disease states that impact oxygen delivery. 2a. Active blood and platelet donors will be sought as study participants since these individuals are familiar with the routines for blood withdrawal and re-infusion. Exclusion Criteria The exclusion criteria is derived from the American Red Cross(ARC) Standard Operating Procedure (SOP) for autologous donation AND the parameters set out in the investigational new drug application (IND). 1. Individuals who are pregnant, breastfeeding, or are unwilling to avoid pregnancy during the study. 2. Individuals with an anatomic anomaly that would increase the risks associated with placement of the vascular catheters. 3. Individuals who report chronic diseases requiring medication of the heart, lungs, kidney, liver, etc or afflicted with any acute or chronic pathology that in the opinion of the screening physician makes them unsuitable for study. 4. Individuals with a recent history of antibiotic therapy (check for underlying cause). 5. Individuals unwilling to refrain from taking any phosphodiesterase 5 (PDE-5) inhibitor for at least 24 h prior to donation and/or autologous transfusion. 6. Individuals taking a vitamin K antagonist (warfarin) or other anticoagulant (e.g. heparin, clopidogrel, enoxaparin or dalteparin). 7. Individuals taking allopurinol, beta-adrenergic blockers, tricyclic antidepressants, meperidine (or related central nervous system (CNS) agents), or nitrates. 8. Individuals on long-term antihistamine therapy 8a. The study physician will determine on a case by case basis the suitability for inclusion of individuals who control seasonal or acute allergies with occasional antihistamine use. 9. Individuals with blood pressure parameters outside the normal range of 90-180 mm Hg systolic and 50-100 mm Hg diastolic. 10. Individuals with heart rates outside the range of 50 to 100 beats per minutes or with a pathologic irregularity. 10a. Pulses lower than 50 may be acceptable if the study participant participates in endurance training. The study physician will be consulted for evaluation. 11. Individuals with an inherited or acquired blood coagulation disorder, congenital methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g. sickle cell). 12. Individuals with any illness that may increase the risks associated with the study. 13. Individuals who previously received blood products to treat an acute condition will be evaluated on a case by case basis. 14. Individuals who report an acute or chronic disease state that may impact oxygen delivery. 15. Individuals with evidence of diminished lung capacity. 16. Individuals who might have difficulty with the placement of a face mask (e.g. claustrophobia, uncontrolled asthma, severe allergies, sensitive skin) and/or the inhalation of a product for approximately 1-2 hr. |
Country | Name | City | State |
---|---|---|---|
United States | University Hospitals Cleveland Medical Center | Cleveland | Ohio |
Lead Sponsor | Collaborator |
---|---|
James Reynolds | Case Western Reserve University, National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Bunn HF, May MH, Kocholaty WF, Shields CE. Hemoglobin function in stored blood. J Clin Invest. 1969 Feb;48(2):311-21. doi: 10.1172/JCI105987. — View Citation
Malone DL, Dunne J, Tracy JK, Putnam AT, Scalea TM, Napolitano LM. Blood transfusion, independent of shock severity, is associated with worse outcome in trauma. J Trauma. 2003 May;54(5):898-905; discussion 905-7. doi: 10.1097/01.TA.0000060261.10597.5C. — View Citation
McMahon TJ, Ahearn GS, Moya MP, Gow AJ, Huang YC, Luchsinger BP, Nudelman R, Yan Y, Krichman AD, Bashore TM, Califf RM, Singel DJ, Piantadosi CA, Tapson VF, Stamler JS. A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14801-6. doi: 10.1073/pnas.0506957102. Epub 2005 Oct 3. — View Citation
Pawloski JR, Hess DT, Stamler JS. Export by red blood cells of nitric oxide bioactivity. Nature. 2001 Feb 1;409(6820):622-6. doi: 10.1038/35054560. — View Citation
Rao SV, Jollis JG, Harrington RA, Granger CB, Newby LK, Armstrong PW, Moliterno DJ, Lindblad L, Pieper K, Topol EJ, Stamler JS, Califf RM. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA. 2004 Oct 6;292(13):1555-62. doi: 10.1001/jama.292.13.1555. — View Citation
Reynolds JD, Ahearn GS, Angelo M, Zhang J, Cobb F, Stamler JS. S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17058-62. doi: 10.1073/pnas.0707958104. Epub 2007 Oct 11. — View Citation
Shah DM, Gottlieb ME, Rahm RL, Stratton HH, Barie PS, Paloski WH, Newell JC. Failure of red blood cell transfusion to increase oxygen transport or mixed venous PO2 in injured patients. J Trauma. 1982 Sep;22(9):741-6. doi: 10.1097/00005373-198209000-00004. — View Citation
Singel DJ, Stamler JS. Chemical physiology of blood flow regulation by red blood cells: the role of nitric oxide and S-nitrosohemoglobin. Annu Rev Physiol. 2005;67:99-145. doi: 10.1146/annurev.physiol.67.060603.090918. — View Citation
Sugerman HJ, Davidson DT, Vibul S, Delivoria-Papadopoulos M, Miller LD, Oski FA. The basis of defective oxygen delivery from stored blood. Surg Gynecol Obstet. 1970 Oct;131(4):733-41. No abstract available. — View Citation
VALTIS DJ. Defective gas-transport function of stored red blood-cells. Lancet. 1954 Jan 16;266(6803):119-24. doi: 10.1016/s0140-6736(54)90978-2. No abstract available. — View Citation
Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, Meier-Hellmann A, Nollet G, Peres-Bota D; ABC (Anemia and Blood Transfusion in Critical Care) Investigators. Anemia and blood transfusion in critically ill patients. JAMA. 2002 Sep 25;288(12):1499-507. doi: 10.1001/jama.288.12.1499. — View Citation
* Note: There are 11 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Oxygenation Defined as change in arterial blood oxygenation | tested by arterial blood oxygen content difference - arterial blood gas (ABG) An ABG is a blood test that measures the acidity, or potential of hydrogen (pH), and the levels of oxygen (O2) and carbon dioxide (CO2) from an artery. The test is used to check the function of the patient's lungs and how well they are able to move oxygen and remove carbon dioxide. The aforementioned five components all have different normal values and represent different aspects of the blood gas. According to the National Institute of Health, typical normal values are: pH: 7.35-7.45 Partial pressure of oxygen (PaO2): 75 to 100 mmHg Partial pressure of carbon dioxide (PaCO2): 35-45 mmHg Bicarbonate (HCO3): 22-26 milliequivalent/Liter (mEqL) Oxygen saturation (O2 Sat): 94-100% |
pre infusion and post infusion (every 3 to 6 hours, for 24 hours) | |
Primary | Oxygenation Defined as change in venous blood oxygenation CO2 ABG vs. VBG: VBG CO2 6mm Hg higher | tested by venous blood oxygen content difference - venous blood gas (VBG). An ABG is a blood test that measures the acidity, or pH, and the levels of oxygen (O2) and carbon dioxide (CO2) from an a vein. The test is used to check the function of the patient's lungs and how well they are able to move oxygen and remove carbon dioxide. pH ABG vs. VBG: VBG pH 0.03-0.05 lower HCO3 ABG vs. VBG: VBG HCO3 1.5-2.0 mEq/L lower CO2 ABG vs. VBG: VBG CO2 6mm Hg higher |
pre infusion and post infusion (every 3 to 6 hours, for 24 h) | |
Primary | Increase in peripheral tissue oxygenation | tested with near infrared spectroscopy. An Infrared spectroscopy (IR spectroscopy or vibrational spectroscopy) involves the interaction of infrared radiation with matter. It covers a range of techniques, mostly based on absorption spectroscopy. As with all spectroscopic techniques, it can be used to identify and study chemicals. |
continuous monitoring from start of transfusion until next morning. Approximately 24 hours |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05699005 -
Individualized or Conventional Transfusion Strategies During Peripheral VA-ECMO
|
Phase 1 | |
Recruiting |
NCT06403163 -
Transfusion Surveillance in Anaesthesia
|
||
Not yet recruiting |
NCT02587845 -
Use of Transexamic Acid in Hip Replacement
|
Phase 3 | |
Completed |
NCT03365999 -
Oral Tranexamic Acid vs. Oral Aminocaproic Acid to Reduce Blood Loss and Transfusion After Total Knee Replacement.
|
Phase 2 | |
Completed |
NCT03784794 -
Patient Blood Management for Massive Obstetric Hemorrhage
|
N/A | |
Not yet recruiting |
NCT02139995 -
West-China Transfusion Score for Critically-ill Patients
|
Phase 3 | |
Completed |
NCT04513249 -
Effects of Therapeutic Plasmaexhange on Viscoelastic Tests in Non-coagulopathic Patients
|
||
Not yet recruiting |
NCT03934112 -
Impact of Transfusional Practice on the Morbidity and Mortality of Patients in Intensive Care Unit
|
||
Completed |
NCT03394274 -
Restrictive Versus Liberal Transfusion, Major Surgeries
|
N/A | |
Not yet recruiting |
NCT06399536 -
Individualized ANH for Non-cardiac Surgery
|
N/A | |
Withdrawn |
NCT04388722 -
Monitoring Noninvasively for Infusion and Transfusion Optimization
|
N/A | |
Completed |
NCT03476005 -
Proficiency Based Training to Investigate WBIT
|
N/A | |
Not yet recruiting |
NCT04413721 -
Effects of Packed Red Blood Cell Storage Duration on Pediatric Living Donor Liver Transplantation
|
N/A | |
Recruiting |
NCT02461264 -
Transfusion Strategy in Hematological Intensive Care Unit
|
Phase 3 | |
Terminated |
NCT01915654 -
Impact of RBC Transfusion Less Than 14 Days on Morbidity and Mortality in Cardiac Surgical Patients
|
N/A | |
Not yet recruiting |
NCT05696210 -
Evaluation of the 1-year Prognosis of Patients Under Veno-arterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock With Blood Transfusion Requirement
|
||
Completed |
NCT04286984 -
Implementation of a Patient Blood Management Program in Gastric Cancer Surgery
|
||
Completed |
NCT03764813 -
Cord Blood Transfusion In Preterm Neonates (CB-TrIP)
|
||
Withdrawn |
NCT04383756 -
Utilization of Donor Whole Blood for Blood Transfusion in Deceased Donor Liver Transplantation
|
Early Phase 1 | |
Completed |
NCT03815773 -
PRospective Multicenter Observational Study on Transfusion Practice in Vv-ECMO Patients: The PROTECMO Study
|