This study is an ancillary (add-on) study to the clinical trial entitled "Effect of Nitric Oxide in Cardiac Surgery Patients With Endothelial Dysfunction", which has Clinical Trials.gov identifier NCT02836899. NCT02836899 trial randomizes cardiac surgical patients to receive either Nitric Oxide (NO) or a placebo during and after cardiac surgery.
This ancillary study aims to assess the effects of Nitric Oxide on plasma reduction-oxidation reactions of patients undergoing cardiac surgery requiring prolonged cardiopulmonary bypass.
Condition or disease | Intervention/treatment | Phase |
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Cardiovascular Diseases Oxidative Stress Endothelial Dysfunction | Drug: Nitrogen Gas for Inhalation Other: Blood withdrawal Drug: Nitric Oxide | Phase 2 |
The endothelial dysfunction is a pathologic process characterized by impaired endothelial nitric oxide (NO) signaling and metabolism leading to decreased vascular response to vasodilation. Cardiac surgical patients affected by multiple cardiovascular risk factors (e.g., hypertension, diabetes, dyslipidemia) commonly present with endothelial dysfunction due to a chronic unbalance of the redox state caused by an increased oxidative stress. Moreover, the use of cardiopulmonary bypass, the hemolysis, the ischemia and the inflammation associated with the surgery magnifies the oxidative stress, which has been shown to contribute to post-operative complications. In order to decrease oxidative stress, several antioxidant drugs and vitamins have been trialed with marginal health benefits.
Recently, different research groups reported that NO delivered during cardiac surgery improved outcomes both in children and adults. Nitric oxide decreased the incidence and the severity of postoperative acute kidney injury, the extension of infarction size, the duration of mechanical ventilation, the length of stay and the use of rescue therapies as postoperative venous-arterial extra-corporeal membrane oxygenation.
The exogenous administration of NO has been shown to prevent the scavenging of endogenous NO by inactivating the highly oxidative-reactive ferrous plasma oxy-hemoglobin to ferric met-hemoglobin. Our group is conducting a randomized controlled trial at Massachusetts General Hospital (Boston, USA) in patients with signs and symptoms of endothelial dysfunction, undergoing cardiac surgery requiring prolonged cardiopulmonary bypass and randomized to receive NO or placebo. However, the mechanisms underlying the effects of NO admistration on plasmatic redox equilibrium have still to be determined. The aim of this ancillary study is (I) to determine the changes of redox state in the plasma of surgical patients receiving either 80 ppm of NO (study group) or Nitrogen (placebo group). (II) To evaluate whether the degree of change in redox state is associated to postoperative complication.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 100 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Basic Science |
Official Title: | Effects of Prolonged Delivery of Nitric Oxide Gas on Plasma Reduction-Oxidation Reactions in Cardiac Surgical Patients |
Actual Study Start Date : | July 25, 2019 |
Estimated Primary Completion Date : | February 28, 2021 |
Estimated Study Completion Date : | July 31, 2022 |
Arm | Intervention/treatment |
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Placebo Comparator: Nitrogen
Inhaled nitrogen will be administered via the cardiopulmonary bypass (CPB) machine and after CPB via the inspiratory limb of the anesthetic or ventilator circuit, and thereafter via the mechanical ventilator in the Intensive Care Unit (ICU). Test gas administration will commence at the onset of CPB and last for 24 hours.
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Drug: Nitrogen Gas for Inhalation
See arm description
Other Name: N2
Other: Blood withdrawal Blood samples will be collected over four time-points: (I) baseline (before surgery) (II) end of the surgery, (III) end of 24 hours of gas delivery and (IV) 24 hours from the gas suspension.
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Experimental: Nitric Oxide
Inhaled nitric oxide (iNO) will be administered via the cardiopulmonary bypass (CPB) machine and after CPB via the inspiratory limb of the anesthetic or ventilator circuit, and thereafter via the mechanical ventilator in the ICU. Test gas administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, inhaled nitric oxide (iNO) will be weaned and discontinued.
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Other: Blood withdrawal
Blood samples will be collected over four time-points: (I) baseline (before surgery) (II) end of the surgery, (III) end of 24 hours of gas delivery and (IV) 24 hours from the gas suspension.
Drug: Nitric Oxide See arm description
Other Name: iNO
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Evidence of hemolysis from any other origin:
a. Intravascular: i. Intrinsic RBC defects leading to hemolytic anemia (eg, enzyme deficiencies, hemoglobinopathies, membrane defects) ii. Extrinsic: liver disease, hypersplenism, infections (eg, bartonella, babesia, malaria), treatment with oxidizing exogenous agents (eg, dapsone, nitrites, aniline dyes), exposure to other hemolytic agents (eg, lead, snake and spider bites), lymphocyte leukemia, autoimmune hemolytic disorders b. Extravascular: Infection (eg, clostridial sepsis, severe malaria), paroxysmal cold hemoglobinuria, cold agglutinin disease, paroxysmal nocturnal hemoglobinuria, iv infusion of Rho(D) immune globulin, iv infusion of hypotonic solutions
Contact: Lorenzo Berra, MD | (617) 643 7733 ext +1 | LBERRA@mgh.harvard.edu | |
Contact: Francesco Zadek, MD | 6178344809 ext +1 | fzadek@mgh.harvard.edu |
United States, Massachusetts | |
Massachusetts General Hospital | Recruiting |
Boston, Massachusetts, United States, 02114 | |
Contact: Lorenzo Berra, MD 617-643-7733 lberra@mgh.harvard.edu | |
United Kingdom | |
MP 825 Southampton General Hospita | Active, not recruiting |
Southampton, Hampshire, United Kingdom, SO16 6YD |
Principal Investigator: | Lorenzo Berra, MD | Massachusett General Hospital |
Tracking Information | |||||||||
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First Submitted Date ICMJE | July 10, 2019 | ||||||||
First Posted Date ICMJE | July 16, 2019 | ||||||||
Last Update Posted Date | November 10, 2020 | ||||||||
Actual Study Start Date ICMJE | July 25, 2019 | ||||||||
Estimated Primary Completion Date | February 28, 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
Changes of concentration in plasma and red blood cells of nitric oxide metabolites after cardiac surgery. [ Time Frame: Plasma will be sampled before the cardiac surgery and after the first 48 hours from surgery ] The investigators will describe the trends in plasma and red blood cells of nitric oxide (NO) metabolites after the surgery. Nitric oxide (NO) metabolites concentrations will be measured using chemiluminescence. The concentrations will be expressed in microMoles.
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Effects of Prolonged Delivery of Nitric Oxide Gas on Plasma Reduction-Oxidation Reactions in Cardiac Surgical Patients | ||||||||
Official Title ICMJE | Effects of Prolonged Delivery of Nitric Oxide Gas on Plasma Reduction-Oxidation Reactions in Cardiac Surgical Patients | ||||||||
Brief Summary |
This study is an ancillary (add-on) study to the clinical trial entitled "Effect of Nitric Oxide in Cardiac Surgery Patients With Endothelial Dysfunction", which has Clinical Trials.gov identifier NCT02836899. NCT02836899 trial randomizes cardiac surgical patients to receive either Nitric Oxide (NO) or a placebo during and after cardiac surgery. This ancillary study aims to assess the effects of Nitric Oxide on plasma reduction-oxidation reactions of patients undergoing cardiac surgery requiring prolonged cardiopulmonary bypass. |
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Detailed Description |
The endothelial dysfunction is a pathologic process characterized by impaired endothelial nitric oxide (NO) signaling and metabolism leading to decreased vascular response to vasodilation. Cardiac surgical patients affected by multiple cardiovascular risk factors (e.g., hypertension, diabetes, dyslipidemia) commonly present with endothelial dysfunction due to a chronic unbalance of the redox state caused by an increased oxidative stress. Moreover, the use of cardiopulmonary bypass, the hemolysis, the ischemia and the inflammation associated with the surgery magnifies the oxidative stress, which has been shown to contribute to post-operative complications. In order to decrease oxidative stress, several antioxidant drugs and vitamins have been trialed with marginal health benefits. Recently, different research groups reported that NO delivered during cardiac surgery improved outcomes both in children and adults. Nitric oxide decreased the incidence and the severity of postoperative acute kidney injury, the extension of infarction size, the duration of mechanical ventilation, the length of stay and the use of rescue therapies as postoperative venous-arterial extra-corporeal membrane oxygenation. The exogenous administration of NO has been shown to prevent the scavenging of endogenous NO by inactivating the highly oxidative-reactive ferrous plasma oxy-hemoglobin to ferric met-hemoglobin. Our group is conducting a randomized controlled trial at Massachusetts General Hospital (Boston, USA) in patients with signs and symptoms of endothelial dysfunction, undergoing cardiac surgery requiring prolonged cardiopulmonary bypass and randomized to receive NO or placebo. However, the mechanisms underlying the effects of NO admistration on plasmatic redox equilibrium have still to be determined. The aim of this ancillary study is (I) to determine the changes of redox state in the plasma of surgical patients receiving either 80 ppm of NO (study group) or Nitrogen (placebo group). (II) To evaluate whether the degree of change in redox state is associated to postoperative complication. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Basic Science |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
100 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | July 31, 2022 | ||||||||
Estimated Primary Completion Date | February 28, 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United Kingdom, United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT04022161 | ||||||||
Other Study ID Numbers ICMJE | RedOx-NO | ||||||||
Has Data Monitoring Committee | No | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Lorenzo Berra, MD, Massachusetts General Hospital | ||||||||
Study Sponsor ICMJE | Massachusetts General Hospital | ||||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Massachusetts General Hospital | ||||||||
Verification Date | November 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |