Study Stopped
Lack of funding
Effects of Prolonged Delivery of Nitric Oxide Gas on Plasma Reduction-Oxidation Reactions in Cardiac Surgical Patients
1 other identifier
interventional
N/A
2 countries
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Jul 2019
Longer than P75 for phase_2 cardiovascular-diseases
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 10, 2019
CompletedFirst Posted
Study publicly available on registry
July 16, 2019
CompletedStudy Start
First participant enrolled
July 25, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 24, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
November 24, 2025
CompletedDecember 2, 2025
November 1, 2025
6.3 years
July 10, 2019
November 24, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Changes in the concentration of glutathione/glutathione disulfide (GSH/GSSG) and the cysteine/ cysteine disulfide (Cys/CysSS) couples in the plasma after cardiac surgery.
The investigators will measure the changes in plasma concentration of GSH, GSSG, Cys, CysSS, of subjects undergoing cardiac surgery with prolonged cardiopulmonary bypass, using ultrahigh-performance liquid chromatography in combination with electrospray-ionization tandem mass spectrometry. The concentration will be expressed in microMoles.
Plasma will be sampled before the cardiac surgery and during the first 48 hours from surgery
Changes in the electrical potential of glutathione/glutathione disulfide (GSH/GSSG) and the cysteine/ cysteine disulfide (Cys/CysSS) couples in the plasma after cardiac surgery.
The investigators will compare the changes of plasma redox state from baseline of patients receiving either 80 ppm of nitric oxide (study group) or nitrogen (placebo group), during cardiac surgery. The redox state will be assessed by measuring the electrical potential of GSH/GSSG and the Cys/CysSS couples in the plasma, using Nerst's equation. The electrical potential will be express in milliVolt.
Plasma will be sampled before the cardiac surgery and during the first 48 hours from surgery
Secondary Outcomes (1)
Changes of concentration in plasma and red blood cells of nitric oxide metabolites after cardiac surgery.
Plasma will be sampled before the cardiac surgery and after the first 48 hours from surgery
Study Arms (2)
Nitrogen
PLACEBO COMPARATORInhaled 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.
Nitric Oxide
EXPERIMENTALInhaled 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- Eligible and randomized in the trial NCT02836899
- Provide written informed consent
- Age ≥ 18 years of age
- Elective cardiac or aortic surgery with CPB \>90 minutes
- Clinical evidence of endothelial dysfunction assessed by a specifically designed questionnaire
You may not qualify if:
- Estimated Glomerular Filtration Rate less than 30 ml/min/1.73 m2
- Emergent cardiac surgery
- Life expectancy \< 1 year at the time of enrollment
- Hemodynamic instability as defined by a systolic blood pressure \<90 mmHg.
- Mean pulmonary artery pressure ≥ 40 mm Hg and PVR \> 4 Wood Units.
- Left ventricular ejection fraction \< 30% by echocardiography obtained within three months of enrollment
- Administration of one or more Packed Red Blood Cell (PRBC) transfusions in the week prior to enrollment
- X-ray contrast infusion less than 48 hours before surgery
- 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 the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
MP 825 Southampton General Hospita
Southampton, Hampshire, SO16 6YD, United Kingdom
Related Publications (2)
Marrazzo F, Spina S, Zadek F, Lama T, Xu C, Larson G, Rezoagli E, Malhotra R, Zheng H, Bittner EA, Shelton K, Melnitchouk S, Roy N, Sundt TM, Riley WD, Williams P, Fisher D, Kacmarek RM, Thompson TB, Bonventre J, Zapol W, Ichinose F, Berra L. Protocol of a randomised controlled trial in cardiac surgical patients with endothelial dysfunction aimed to prevent postoperative acute kidney injury by administering nitric oxide gas. BMJ Open. 2019 Jul 4;9(7):e026848. doi: 10.1136/bmjopen-2018-026848.
PMID: 31278097BACKGROUNDSutton TR, Minnion M, Barbarino F, Koster G, Fernandez BO, Cumpstey AF, Wischmann P, Madhani M, Frenneaux MP, Postle AD, Cortese-Krott MM, Feelisch M. A robust and versatile mass spectrometry platform for comprehensive assessment of the thiol redox metabolome. Redox Biol. 2018 Jun;16:359-380. doi: 10.1016/j.redox.2018.02.012. Epub 2018 Feb 19.
PMID: 29627744BACKGROUND
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lorenzo Berra, MD
Massachusett General Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Lorenzo Berra, MD, Associate Professor of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School
Study Record Dates
First Submitted
July 10, 2019
First Posted
July 16, 2019
Study Start
July 25, 2019
Primary Completion
November 24, 2025
Study Completion
November 24, 2025
Last Updated
December 2, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will not share