InflammationPhase 2/3NCT03455218
Nitric Oxide Administration During Pediatric Cardiopulmonary Bypass Surgery to Prevent Platelet Activation
A Phase 2/3 study testing Nitric Oxide and INOmax in people with Inflammation and Platelet Dysfunction, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
Open heart surgery requires the use of a cardiopulmonary bypass (CPB) circuit. As blood flows across the artificial surfaces of the CPB circuit, platelets are activated and consumed. This activation results in a profound inflammatory reaction and need for transfusion. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Inflammation, Platelet Dysfunction
- What is being tested?
- Nitric Oxide and INOmax
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2018to 5 May 2019
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants less than one year of age
- Undergoing cardiac surgery with the use of cardiopulmonary bypass
Who cannot join
- Prior surgery requiring CPB within the same hospitalization
- Pre-operative need for extracorporeal membrane oxygenation or mechanical circulatory support
- Known hypersensitivity to nitric oxide
- Known hemostatic or thrombotic disorder that results in an altered transfusion/anticoagulation protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Nitric Oxide Administration During Pediatric Cardiopulmonary Bypass Surgery to Prevent Platelet activation-a Single Center Pilot Study
Open heart surgery requires the use of a cardiopulmonary bypass (CPB) circuit. As blood flows across the artificial surfaces of the CPB circuit, platelets are activated and consumed. This activation results in a profound inflammatory reaction and need for transfusion. This reaction is intensified in younger, smaller patients undergoing longer, more complex open heart surgery. Nitric oxide is naturally released by vascular endothelial surfaces and acts as a signaling molecule which prevents platelet activation. The investigators hypothesize that the addition of the nitric oxide to the sweep gas of the oxygenator during cardiopulmonary bypass surgery will replace this natural endothelial function and thus prevent platelet activation and consumption. The investigators plan to test this hypothesis with a pilot double blinded, randomized trial of 40 patients less than a year of age undergoing cardiac surgery requiring CPB.
Read the detailed description
Open heart surgery requires the use of a CPB circuit. As blood flows across the artificial surfaces of the CPB circuit, platelets are consumed (1). The investigators recently completed a prospective observational trial of neonates undergoing cardiac surgery requiring CPB. In this trial the investigators demonstrated a dramatic decrease in platelet count from baseline to intraoperatively. The platelet count rebounded with transfusion and normalized by the time of admission to the cardiac intensive care unit (CICU). Despite prophylactic transfusion of blood products to all patients, 41% experienced excessive postoperative bleeding (defined in terms of chest tube output and need for reoperation).
Further investigation by Dr. Debra Newman in her lab at the Blood Research Institute delineated the platelet defect associated with CPB in the neonates more clearly. Dr. Newman found a significant decrease in the platelet responsiveness to thrombin receptor activating protein (TRAP), thromboxane A2 analog (U46619), and collagen-related peptide (CRP). Further analysis revealed that the effect of CPB on platelet responsiveness to TRAP and U46619 is likely dependent on its effect on platelet count, whereas CPB affects platelet responsiveness to CRP independently of platelet count.
In children, postoperative blood loss and transfusion of blood products has been shown to contribute significantly to the morbidity and mortality of surgeries that require CPB (2, 3). In addition to the need for blood product replacement, the activation of platelets contributes to the intense inflammatory reaction seen in surgeries requiring CPB (4). Patients with a less intense inflammatory response post-operatively generally do better with less morbidity (5).
The oxygenator membrane surface of the CPB pump is a large contributor to the surface area of CPB circuit. As a major contributor to the surface area of the circuit and the location of the gas interface, the oxygenator is a significant contributor to the hemostatic and inflammatory stimulus of CPB. Advances in oxygenator technology have modified the surface to prevent interaction with the blood, but no artificial surface has been found to be as inert as the natural endothelium of the vasculature (5).
A major mechanism by which endothelial surfaces inhibit activation of platelets is by producing nitric oxide (6). Nitric oxide is lipophilic and traverses cellular membranes where it acts on intracellular signaling pathways in platelets to prevent platelet activation and aggregation (7). The artificial surface of the CPB pump does not produce nitric oxide and hence is devoid of this potent inhibitor of platelet activation.
In multiple experimental ex-vivo models of CPB, the addition of nitric oxide to the sweep gas of the oxygenator resulted in preserved platelet counts, preserved platelet function, and decreased markers of platelet activation (8-11).
Multiple clinical trials of nitric oxide administration during CPB have shown positive results. Chung et al. showed in a group of 41 adults undergoing coronary artery surgery requiring CPB that the addition of nitric oxide to the oxygenator resulted in a preservation of platelet numbers, a decrease in markers of platelet activation, and less post-operative blood loss (12). Checchia et al. investigated the effect of nitric oxide in a group of sixteen infants undergoing repair of tetralogy of Fallot and found the patients treated with nitric oxide had an improvement in clinical outcomes of length of stay in the intensive care unit and number of hours requiring mechanical ventilation (13). James et al. showed a 50% decrease in the incidence of low cardiac output syndrome in a randomized trial of 198 children. The effect was most profound in the younger children and those undergoing the most complex repairs (14). These patients are also the ones demonstrated to have the most intense inflammatory reaction postoperatively (15).
Despite these promising studies, several questions remain. The mechanism of platelet preservation has not been delineated. The collaboration between clinicians at Children's Hospital of Wisconsin and Dr. Newman at the Blood Center of Wisconsin has been established and has experience in investigating the effects of CPB on platelets in infants. This collaboration is poised to help define the mechanism of nitric oxide in preserving platelet function during CPB in infants. All studies to date have been single center and underpowered to investigate clinical outcomes of interest such as mortality and length of hospital stay. Dr. Niebler has begun to assemble a multi-center study team. Local data is necessary to help guide the power calculation in determining the sample size for this larger study and to demonstrate the capabilities of the local institution in leading a trial of this magnitude.
- Conditions
- Inflammation, Platelet Dysfunction
- Being tested
- Nitric Oxide, Placebo, INOmax
- Keywords
- Cardiopulmonary Bypass, Infant, Nitric Oxide, Thrombocytopenia, Blood Platelets
- Medical subject headings
- Inflammation, Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
Also called INOmax
20 ppm of Nitric Oxide gas delivered to the oxygenator for the duration of cardiopulmonary bypass
PlaceboDrug
INOmax device connected to oxygenator, but no gas is delivered
INOmaxDevice
Also called inhaled nitric oxide delivery device
All patients will have the INOmax device connected to the oxygenator
| Study group | Role | What they receive |
|---|---|---|
| Nitric Oxide | Experimental | 20 ppm of Nitric Oxide delivered to the oxygenator via the INOmax device for the duration of the cardiopulmonary bypass time Receives: Drug: Nitric Oxide; Device: INOmax |
| Placebo | Placebo comparator | INOmax device attached to the oxygenator, but no gas is delivered through the device Receives: Drug: Placebo; Device: INOmax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Platelet Count
Change in platelet count from baseline to conclusion of cardiopulmonary bypass = (Platelet count at end of CPB) - (Platelet count prior to start of CPB)
Measured: From baseline to end of cardiopulmonary bypass (2-6 hours)
30 Day Mortality
30 day all cause mortality
Measured: 30 days
Hospital Length of Stay
Length of stay in the hospital following the operation
Measured: 6 months
Methemoglobin Level Pre-CPB
Methemoglobin levels in the blood measured at baseline
Measured: 24 hours
Methemoglobin Level-End of CPB
Methemoglobin Level obtained at the end of cardiopulmonary bypass
Measured: 4 hours
Methemoglobin Level-ICU Admit
Methemoglobin level obtained at the time of ICU Admit
Measured: 24 hours
Secondary outcomes (10)
Change in Platelet Response to TRAP as Measured by P-selectin Expression
The P-selectin expression measured as a mean florescence was measured in platelets stimulated with thrombin receptor activating protein (TRAP) was measured at baseline and at conclusion of cardiopulmonary bypass. Mean of each assessment measured multiple times at each time point. Median change values were reported. The change in these values is the outcome measure = (Platelet response to TRAP at end of CPB) - (Platelet response to TRAP prior to CPB)
Measured: From baseline to end of cardiopulmonary bypass (2-6 hours)
Change in Platelet Response to U46619 as Measured by P-selectin Expression
The P-selectin expression measured as a mean florescence was measured in platelets stimulated with U46619 was measured at baseline and at conclusion of cardiopulmonary bypass. Mean of each assessment measured multiple times at each time point. Median change values were reported. The change in these values is the outcome measure = (Platelet response to U46619 at end of CPB) - (Platelet response to U46619 prior to CPB)
Measured: From baseline to end of cardiopulmonary bypass (2-6 hours)
Change in Platelet Response to CRP as Measured by P-selectin Expression
The P-selectin expression measured as a mean florescence was measured in platelets stimulated with CRP was measured at baseline and at conclusion of cardiopulmonary bypass. Mean of each assessment measured multiple times at each time point. Median change values were reported. The change in these values is the outcome measure = (Platelet response to CRP at end of CPB) - (Platelet response to CRP prior to CPB)
Measured: From baseline to end of cardiopulmonary bypass (2-6 hours)
Volume of Platelet Transfusion
Volume per kg of platelet transfusion given to patient from the conclusion of cardiopulmonary bypass to 48 hours post-operatively
Measured: 48 hours post-operatively
Volume of Packed Red Blood Cell Transfusion
Volume per kg of packed red blood cell transfusion given to patient from the conclusion of cardiopulmonary bypass to 48 hours post-operatively
Measured: 48 hours post-operatively
Transfusion Exposures
Total number of transfusion exposures for a patient from the conclusion of cardiopulmonary bypass to 48 hours post-operatively
Measured: 48 hours post-operatively
Length of Mechanical Ventilation
Time (days) spent on ventilator following the operation
Measured: 30 days post-operatively
Vasoactive Infusion Score
Highest vasoactive infusion score (VIS) within 24 hours post-operatively. Vasoactive infusion score is based on the dose of the vasoactive infusions the patient is given VIS = Dopamine dose (μg/kg/min) + Dobutamine dose (μg/kg/min) +100 × epinephrine dose (μg/kg/min) + 10 X Milrinone dose (μg/kg/min) +10,000 × Vasopressin dose (U/kg/min) + 100 × Norepinephrine dose (μg/kg/min).
The minimum value is 0 if the patient is not on any vasoactive medications. There is no "maximum" score as there is no "maximum" dose of vasoactive medications. Higher scores indicate that the patient is on more vasoactive medications which is generally considered worse.
Measured: 24 hours post-operatively
Number of Subjects Requiring Extracorporeal Membrane Oxygenation
Dichotomous outcome-required extracorporeal membrane oxygenation within 48 hours post-operatively
Measured: 48 hours post-operatively
Hospital Cost
Total hospital cost at the time of discharge
Measured: 6 months post-operatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2018
- Study start25 Apr 2018
- Primary completion20 Apr 2019
- Study completion5 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for InflammationStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Double Blinded, Placebo Controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt, Clinical & Translational Science Institute of Southeast Wisconsin, Versiti Blood Health
- Responsible party
- Principal investigator, Robert Niebler, MD, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03455218
- Sponsor's protocol ID
- 1111115-1NO in CPB 001
- Status last verified
- Jul 2020
- First submitted
- 6 Feb 2018
- Last updated
- 13 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: we are willing to share the IPD if requested by another investigator. Please contact the principle investigator if interested
Publications
Despotis GJ, Avidan MS, Hogue CW Jr. Mechanisms and attenuation of hemostatic activation during extracorporeal circulation. Ann Thorac Surg. 2001 Nov;72(5):S1821-31. doi: 10.1016/s0003-4975(01)03211-8.
PubMed 11722116Chambers LA, Cohen DM, Davis JT. Transfusion patterns in pediatric open heart surgery. Transfusion. 1996 Feb;36(2):150-4. doi: 10.1046/j.1537-2995.1996.36296181928.x.
PubMed 8614966Petaja J, Lundstrom U, Leijala M, Peltola K, Siimes MA. Bleeding and use of blood products after heart operations in infants. J Thorac Cardiovasc Surg. 1995 Mar;109(3):524-9. doi: 10.1016/S0022-5223(95)70284-9.
PubMed 7877314Rinder CS, Bonan JL, Rinder HM, Mathew J, Hines R, Smith BR. Cardiopulmonary bypass induces leukocyte-platelet adhesion. Blood. 1992 Mar 1;79(5):1201-5.
PubMed 1371416Wan 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 9315800Radomski MW, Vallance P, Whitley G, Foxwell N, Moncada S. Platelet adhesion to human vascular endothelium is modulated by constitutive and cytokine induced nitric oxide. Cardiovasc Res. 1993 Jul;27(7):1380-2. doi: 10.1093/cvr/27.7.1380.
PubMed 7504587Naseem KM, Roberts W. Nitric oxide at a glance. Platelets. 2011;22(2):148-52. doi: 10.3109/09537104.2010.522629. Epub 2010 Nov 4.
PubMed 21050056Annich GM, Meinhardt JP, Mowery KA, Ashton BA, Merz SI, Hirschl RB, Meyerhoff ME, Bartlett RH. Reduced platelet activation and thrombosis in extracorporeal circuits coated with nitric oxide release polymers. Crit Care Med. 2000 Apr;28(4):915-20. doi: 10.1097/00003246-200004000-00001.
PubMed 10809259de Graaf JC, Banga JD, Moncada S, Palmer RM, de Groot PG, Sixma JJ. Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. Circulation. 1992 Jun;85(6):2284-90. doi: 10.1161/01.cir.85.6.2284.
PubMed 1591842Konishi R, Shimizu R, Firestone L, Walters FR, Wagner WR, Federspiel WJ, Konishi H, Hattler BG. Nitric oxide prevents human platelet adhesion to fiber membranes in whole blood. ASAIO J. 1996 Sep-Oct;42(5):M850-3. doi: 10.1097/00002480-199609000-00111.
PubMed 8945004Mellgren K, Friberg LG, Mellgren G, Hedner T, Wennmalm A, Wadenvik H. Nitric oxide in the oxygenator sweep gas reduces platelet activation during experimental perfusion. Ann Thorac Surg. 1996 Apr;61(4):1194-8. doi: 10.1016/0003-4975(96)00017-3.
PubMed 8607682Chung A, Wildhirt SM, Wang S, Koshal A, Radomski MW. Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: a pilot clinical study. J Thorac Cardiovasc Surg. 2005 Apr;129(4):782-90. doi: 10.1016/j.jtcvs.2004.06.049.
PubMed 15821644Checchia PA, Bronicki RA, Muenzer JT, Dixon D, Raithel S, Gandhi SK, Huddleston CB. Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children--a randomized trial. J Thorac Cardiovasc Surg. 2013 Sep;146(3):530-6. doi: 10.1016/j.jtcvs.2012.09.100. Epub 2012 Dec 8.
PubMed 23228403James C, Millar J, Horton S, Brizard C, Molesworth C, Butt W. Nitric oxide administration during paediatric cardiopulmonary bypass: a randomised controlled trial. Intensive Care Med. 2016 Nov;42(11):1744-1752. doi: 10.1007/s00134-016-4420-6. Epub 2016 Sep 30.
PubMed 27686343Eisses MJ, Chandler WL. Cardiopulmonary bypass parameters and hemostatic response to cardiopulmonary bypass in infants versus children. J Cardiothorac Vasc Anesth. 2008 Feb;22(1):53-9. doi: 10.1053/j.jvca.2007.06.006. Epub 2007 Aug 22.
PubMed 18249331
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitric Oxide Administration During Pediatric Cardiopulmonary Bypass Surgery to Prevent Platelet activation-a Single Center Pilot Study
- ClinicalTrials.gov ID
- NCT03455218
- Acronym / sponsor ID
- 1111115-1NO in CPB 001
- Conditions
- Inflammation, Platelet Dysfunction
- Keywords
- Cardiopulmonary Bypass, Infant, Nitric Oxide, Thrombocytopenia, Blood Platelets
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- Mallinckrodt, Clinical & Translational Science Institute of Southeast Wisconsin, Versiti Blood Health
- Study start
- 25 Apr 2018 (actual)
- Primary completion
- 20 Apr 2019 (actual)
- Study completion
- 5 May 2019 (actual)
- First posted
- 6 Mar 2018 (actual)
- Results
- Posted 13 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open heart surgery requires the use of a cardiopulmonary bypass (CPB) circuit. As blood flows across the artificial surfaces of the CPB circuit, platelets are activated and consumed. This activation results in a profound inflammatory reaction and need for transfusion. This reaction is intensified in younger, smaller patients undergoing longer, more complex open heart surgery. Nitric oxide is naturally released by vascular endothelial surfaces and acts as a signaling molecule which prevents platelet activation. The investigators hypothesize that the addition of the nitric oxide to the sweep gas of the oxygenator during cardiopulmonary bypass surgery will replace this natural endothelial function and thus prevent platelet activation and consumption. The investigators plan to test this hypothesis with a pilot double blinded, randomized trial of 40 patients less than a year of age undergoing cardiac surgery requiring CPB.
Detailed description
Open heart surgery requires the use of a CPB circuit. As blood flows across the artificial surfaces of the CPB circuit, platelets are consumed (1). The investigators recently completed a prospective observational trial of neonates undergoing cardiac surgery requiring CPB. In this trial the investigators demonstrated a dramatic decrease in platelet count from baseline to intraoperatively. The platelet count rebounded with transfusion and normalized by the time of admission to the cardiac intensive care unit (CICU). Despite prophylactic transfusion of blood products to all patients, 41% experienced excessive postoperative bleeding (defined in terms of chest tube output and need for reoperation).
Further investigation by Dr. Debra Newman in her lab at the Blood Research Institute delineated the platelet defect associated with CPB in the neonates more clearly. Dr. Newman found a significant decrease in the platelet responsiveness to thrombin receptor activating protein (TRAP), thromboxane A2 analog (U46619), and collagen-related peptide (CRP). Further analysis revealed that the effect of CPB on platelet responsiveness to TRAP and U46619 is likely dependent on its effect on platelet count, whereas CPB affects platelet responsiveness to CRP independently of platelet count.
In children, postoperative blood loss and transfusion of blood products has been shown to contribute significantly to the morbidity and mortality of surgeries that require CPB (2, 3). In addition to the need for blood product replacement, the activation of platelets contributes to the intense inflammatory reaction seen in surgeries requiring CPB (4). Patients with a less intense inflammatory response post-operatively generally do better with less morbidity (5).
The oxygenator membrane surface of the CPB pump is a large contributor to the surface area of CPB circuit. As a major contributor to the surface area of the circuit and the location of the gas interface, the oxygenator is a significant contributor to the hemostatic and inflammatory stimulus of CPB. Advances in oxygenator technology have modified the surface to prevent interaction with the blood, but no artificial surface has been found to be as inert as the natural endothelium of the vasculature (5).
A major mechanism by which endothelial surfaces inhibit activation of platelets is by producing nitric oxide (6). Nitric oxide is lipophilic and traverses cellular membranes where it acts on intracellular signaling pathways in platelets to prevent platelet activation and aggregation (7). The artificial surface of the CPB pump does not produce nitric oxide and hence is devoid of this potent inhibitor of platelet activation.
In multiple experimental ex-vivo models of CPB, the addition of nitric oxide to the sweep gas of the oxygenator resulted in preserved platelet counts, preserved platelet function, and decreased markers of platelet activation (8-11).
Multiple clinical trials of nitric oxide administration during CPB have shown positive results. Chung et al. showed in a group of 41 adults undergoing coronary artery surgery requiring CPB that the addition of nitric oxide to the oxygenator resulted in a preservation of platelet numbers, a decrease in markers of platelet activation, and less post-operative blood loss (12). Checchia et al. investigated the effect of nitric oxide in a group of sixteen infants undergoing repair of tetralogy of Fallot and found the patients treated with nitric oxide had an improvement in clinical outcomes of length of stay in the intensive care unit and number of hours requiring mechanical ventilation (13). James et al. showed a 50% decrease in the incidence of low cardiac output syndrome in a randomized trial of 198 children. The effect was most profound in the younger children and those undergoing the most complex repairs (14). These patients are also the ones demonstrated to have the most intense inflammatory reaction postoperatively (15).
Despite these promising studies, several questions remain. The mechanism of platelet preservation has not been delineated. The collaboration between clinicians at Children's Hospital of Wisconsin and Dr. Newman at the Blood Center of Wisconsin has been established and has experience in investigating the effects of CPB on platelets in infants. This collaboration is poised to help define the mechanism of nitric oxide in preserving platelet function during CPB in infants. All studies to date have been single center and underpowered to investigate clinical outcomes of interest such as mortality and length of hospital stay. Dr. Niebler has begun to assemble a multi-center study team. Local data is necessary to help guide the power calculation in determining the sample size for this larger study and to demonstrate the capabilities of the local institution in leading a trial of this magnitude.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, Double Blinded, Placebo Controlled
| Arm | Type | Receives |
|---|---|---|
| Nitric Oxide | Experimental | Drug: Nitric Oxide, Device: INOmax20 ppm of Nitric Oxide delivered to the oxygenator via the INOmax device for the duration of the cardiopulmonary bypass time |
| Placebo | Placebo comparator | Drug: Placebo, Device: INOmaxINOmax device attached to the oxygenator, but no gas is delivered through the device |
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Infants less than one year of age
- Undergoing cardiac surgery with the use of cardiopulmonary bypass
Key exclusion criteria (4 listed)
- Prior surgery requiring CPB within the same hospitalization
- Pre-operative need for extracorporeal membrane oxygenation or mechanical circulatory support
- Known hypersensitivity to nitric oxide
- Known hemostatic or thrombotic disorder that results in an altered transfusion/anticoagulation protocol
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 |
|---|---|---|
| Nitric OxideAlso: INOmax20 ppm of Nitric Oxide gas delivered to the oxygenator for the duration of cardiopulmonary bypass | Drug | Nitric Oxide |
| PlaceboINOmax device connected to oxygenator, but no gas is delivered | Drug | Placebo |
| INOmaxAlso: inhaled nitric oxide delivery deviceAll patients will have the INOmax device connected to the oxygenator | Device | Nitric Oxide, Placebo |
Primary outcome
Change in Platelet Count
Time frame: From baseline to end of cardiopulmonary bypass (2-6 hours)
Change in platelet count from baseline to conclusion of cardiopulmonary bypass = (Platelet count at end of CPB) - (Platelet count prior to start of CPB)
30 Day Mortality
Time frame: 30 days
30 day all cause mortality
Hospital Length of Stay
Time frame: 6 months
Length of stay in the hospital following the operation
Methemoglobin Level Pre-CPB
Time frame: 24 hours
Methemoglobin levels in the blood measured at baseline
Methemoglobin Level-End of CPB
Time frame: 4 hours
Methemoglobin Level obtained at the end of cardiopulmonary bypass
Methemoglobin Level-ICU Admit
Time frame: 24 hours
Methemoglobin level obtained at the time of ICU Admit
10 secondary outcomes
Change in Platelet Response to TRAP as Measured by P-selectin Expression
Time frame: From baseline to end of cardiopulmonary bypass (2-6 hours)
Change in Platelet Response to U46619 as Measured by P-selectin Expression
Time frame: From baseline to end of cardiopulmonary bypass (2-6 hours)
Change in Platelet Response to CRP as Measured by P-selectin Expression
Time frame: From baseline to end of cardiopulmonary bypass (2-6 hours)
Volume of Platelet Transfusion
Time frame: 48 hours post-operatively
Volume of Packed Red Blood Cell Transfusion
Time frame: 48 hours post-operatively
Transfusion Exposures
Time frame: 48 hours post-operatively
Length of Mechanical Ventilation
Time frame: 30 days post-operatively
Vasoactive Infusion Score
Time frame: 24 hours post-operatively
Number of Subjects Requiring Extracorporeal Membrane Oxygenation
Time frame: 48 hours post-operatively
Hospital Cost
Time frame: 6 months post-operatively
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11722116Despotis GJ, Avidan MS, Hogue CW Jr. Mechanisms and attenuation of hemostatic activation during extracorporeal circulation. Ann Thorac Surg. 2001 Nov;72(5):S1821-31. doi: 10.1016/s0003-4975(01)03211-8.
- Background: PubMed 8614966Chambers LA, Cohen DM, Davis JT. Transfusion patterns in pediatric open heart surgery. Transfusion. 1996 Feb;36(2):150-4. doi: 10.1046/j.1537-2995.1996.36296181928.x.
- Background: PubMed 7877314Petaja J, Lundstrom U, Leijala M, Peltola K, Siimes MA. Bleeding and use of blood products after heart operations in infants. J Thorac Cardiovasc Surg. 1995 Mar;109(3):524-9. doi: 10.1016/S0022-5223(95)70284-9.
- Background: PubMed 1371416Rinder CS, Bonan JL, Rinder HM, Mathew J, Hines R, Smith BR. Cardiopulmonary bypass induces leukocyte-platelet adhesion. Blood. 1992 Mar 1;79(5):1201-5.
- 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 7504587Radomski MW, Vallance P, Whitley G, Foxwell N, Moncada S. Platelet adhesion to human vascular endothelium is modulated by constitutive and cytokine induced nitric oxide. Cardiovasc Res. 1993 Jul;27(7):1380-2. doi: 10.1093/cvr/27.7.1380.
- Background: PubMed 21050056Naseem KM, Roberts W. Nitric oxide at a glance. Platelets. 2011;22(2):148-52. doi: 10.3109/09537104.2010.522629. Epub 2010 Nov 4.
- Background: PubMed 10809259Annich GM, Meinhardt JP, Mowery KA, Ashton BA, Merz SI, Hirschl RB, Meyerhoff ME, Bartlett RH. Reduced platelet activation and thrombosis in extracorporeal circuits coated with nitric oxide release polymers. Crit Care Med. 2000 Apr;28(4):915-20. doi: 10.1097/00003246-200004000-00001.
- Background: PubMed 1591842de Graaf JC, Banga JD, Moncada S, Palmer RM, de Groot PG, Sixma JJ. Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. Circulation. 1992 Jun;85(6):2284-90. doi: 10.1161/01.cir.85.6.2284.
- Background: PubMed 8945004Konishi R, Shimizu R, Firestone L, Walters FR, Wagner WR, Federspiel WJ, Konishi H, Hattler BG. Nitric oxide prevents human platelet adhesion to fiber membranes in whole blood. ASAIO J. 1996 Sep-Oct;42(5):M850-3. doi: 10.1097/00002480-199609000-00111.
- Background: PubMed 8607682Mellgren K, Friberg LG, Mellgren G, Hedner T, Wennmalm A, Wadenvik H. Nitric oxide in the oxygenator sweep gas reduces platelet activation during experimental perfusion. Ann Thorac Surg. 1996 Apr;61(4):1194-8. doi: 10.1016/0003-4975(96)00017-3.
- Background: PubMed 15821644Chung A, Wildhirt SM, Wang S, Koshal A, Radomski MW. Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: a pilot clinical study. J Thorac Cardiovasc Surg. 2005 Apr;129(4):782-90. doi: 10.1016/j.jtcvs.2004.06.049.
- Individual participant dataSharing planned: Undecided. we are willing to share the IPD if requested by another investigator. Please contact the principle investigator if interested
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Nitric Oxide and INOmax in people with Inflammation and Platelet Dysfunction, run by Medical College of Wisconsin at 1 site in United States.
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 4 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 13 Aug 2020. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Platelet Count (time frame: From baseline to end of cardiopulmonary bypass (2-6 hours)). 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 NCT03455218, which also lists 18 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 13 Aug 2020.