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Heart Valve DiseasesPhase 1/2NCT01802619

Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass.

A Phase 1/2 study testing inhaled nitric oxide and inhaled Nitrogen in people with Heart Valve Diseases and Heart; Complications, Valve, Prosthesis, run by Xijing Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Prolonged periods of cardiopulmonary bypass (CPB) cause high levels of plasma free haemoglobin(Hb) and are associated with increased morbidity. We hypothesized that repletion of nitric oxide (NO) during and after the surgical procedure on CPB may protect against endothelium dysfunction and organ failure caused by… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
inhaled nitric oxide and inhaled Nitrogen
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
217 participants
Where
1 siteChina
Study dates
Aug 2013to Jun 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provide written informed consent
  • Are > 18 years of age
  • Elective cardiac or aortic surgery with CPB, when the surgeon plans double valve replacement.
  • Stable pre-operative renal function, without dialysis.

Who cannot join

  • Emergent cardiac surgery
  • Life expectancy < 1 year
  • Hemodynamic instability as defined by a systolic blood pressure <90 mmHg
  • Administration of ≥1 Packed Red Blood Cell transfusion in the week before surgery
  • X-ray contrast infusion less than 1 week before surgery
  • Anticipate administration of nephrotoxic agents, such as hydroxyethyl starch
  • Evidence of intravascular or extravascular hemolysis

Trial locations and contacts

1 site in 1 country.

China1 site

  • Xijing Hospital

    Xi'an, Shaanxi, 710032

Other trials in China

About this study

Official title: Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass: A Double Blind Randomized Controlled Trial.

Prolonged periods of cardiopulmonary bypass (CPB) cause high levels of plasma free haemoglobin(Hb) and are associated with increased morbidity. We hypothesized that repletion of nitric oxide (NO) during and after the surgical procedure on CPB may protect against endothelium dysfunction and organ failure caused by plasma-Hb induced NO scavenging.

Read the detailed description

Prolonged periods of cardiopulmonary bypass (CPB) cause high levels of plasma free haemoglobin(Hb) and are associated with increased morbidity. We hypothesized that repletion of nitric oxide (NO) during and after the surgical procedure on CPB may protect against endothelium dysfunction and organ failure caused by plasma-Hb induced NO scavenging. There are three possible beneficial mechanisms of delivering NO:

  1. Nitric oxide reduces ischemia-reperfusion injury (such as in acute myocardial infarction, stroke, and acute tubular necrosis).
  2. Nitric oxide has anti-inflammatory properties. As antioxidants, exogenous NO may reduce injury by counteracting the cytotoxic effects of reactive oxygen species, modulating leukocyte recruitment, edema formation and tissue disruption.
  3. Exogenous nitric oxide prevents noxious effects of hemolysis-associated NO dysregulation. During hemolysis, nitric oxide gas oxidized of plasma oxyhemoglobin to methemoglobin, thereby inhibiting endogenous endothelium NO scavenging by cell-free Hb.

NO depletion during hemolysis and its sequelae. The release of plasma free Hb (with Fe2+ iron) by hemolysis avidly scavenges nitric oxide (NO) by the dioxygenation reaction. Elevated plasma ferrous Hb levels can induce a "NO deficiency" state. Reduced vascular nitric oxide levels can contribute to vasoconstriction, inflammation, and thrombosis, potentially contributing to systemic endothelial dysfunction after cardiac surgery with CPB.

Being tested
inhaled nitric oxide, inhaled Nitrogen
Medical subject headings
Heart Valve Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • inhaled nitric oxideOther

    Nitric oxide administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, inhaled NO will be weaned and discontinued while carefully monitoring hemodynamics for a period of 2-4 hours.

  • inhaled NitrogenOther

    Standard gas including nitrogen (the vehicle of the Nitric oxide) administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, inhaled gases will be weaned and discontinued while carefully monitoring hemodynamics for a period of 2-4 hours.

Study groups in NCT01802619
Study groupRoleWhat they receive
inhaled nitrogenPlacebo comparatorUsing an Inovent (Ikaria Inc, N.J., USA) or volumetrically-calibrated flowmeters, pure nitrogen (placebo) is mixed with pure O2 or air. During CPB the gas mixture is delivered through the extracorporeal oxygenator, after CPB the NO is delivered through the inspiratory limb of the anesthetic or ventilator circuit.
Receives: Other: inhaled Nitrogen
inhaled nitric oxideExperimentalUsing an Inovent (Ikaria Inc, N.J., USA) or volumetrically-calibrated flowmeters, 800 ppm NO gas is mixed with pure O2 or air to obtain a final concentration of 80 ppm NO. During CPB the gas mixture is delivered through the extracorporeal oxygenator, after CPB the gas is delivered through the inspiratory limb of the anesthetic or ventilator circuit. NO, NO2 and O2 and methemoglobin levels are monitored by an unblinded observer.
Receives: Other: inhaled nitric oxide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. acute kidney injury

    acute kidney injury was defined by the KDIGO criteria

    Measured: an increase of serum creatinine by 50% within 7 days after surgery, or an increase of serum creatinine by 0.3 mg/dl within 2 days after surgery

Secondary outcomes (7)

  1. Chronic kidney disease

    defined as eGFR<60 mL/min/1.73m2

    Measured: at 30 days, 90 days, and 1 year following ICU admission

  2. Loss of 25% of eGFR compared to baseline

    Loss of 25% of eGFR compared to baseline

    Measured: at 30 days, 90 days, and 1 year following ICU admission

  3. Major adverse kidney events (MAKE)

    a composite outcome of loss of 25% of eGFR from baseline, end stage renal disease requiring a continuous renal replacement therapy and mortality.

    Measured: at 30 days, 90 days, and 1 year following ICU admission

  4. Renal Replacement Therapy

    the incidence of need for Renal Replacement Therapy

    Measured: at 30 days, 90 days, and 1 year following ICU admission

  5. Incidence of nonfatal stroke and nonfatal myocardial infarction.

    Nonfatal stroke will be assessed by the NIH Stroke Scale at baseline before surgery and at 28 days, 60 days, 90 days and 1 year after surgery.

    Nonfatal myocardial infarction is defined by the third universal definition of MI released in 2012 by the ESC/ACCF/AHA/WHF.

    Measured: at 30 days, 90 days, and 1 year following ICU admission

  6. Quality of life

    The quality of life will be evaluated by the Katz Index of In dependence in Activities of Daily living

    Measured: at 30 days, 90 days, and 1 year following ICU admission

  7. overall mortality

    all cause mortality

    Measured: at 30 days, 90 days, and 1 year following ICU admission

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2013 (estimated)
  2. Study startAug 2013
  3. Primary completionJun 2015
  4. Study completionJun 2016

Resources

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 1/2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
217 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01802619
Sponsor's protocol ID
20121025-8
Other IDs
81000232
Status last verified
Feb 2018
First submitted
25 Feb 2013
Last updated
13 Feb 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Hu J, Rezoagli E, Zadek F, Bittner EA, Lei C, Berra L. Free Hemoglobin Ratio as a Novel Biomarker of Acute Kidney Injury After On-Pump Cardiac Surgery: Secondary Analysis of a Randomized Controlled Trial. Anesth Analg. 2021 Jun 1;132(6):1548-1558. doi: 10.1213/ANE.0000000000005381.

    PubMed 33481401

  • Lei C, Berra L, Rezoagli E, Yu B, Dong H, Yu S, Hou L, Chen M, Chen W, Wang H, Zheng Q, Shen J, Jin Z, Chen T, Zhao R, Christie E, Sabbisetti VS, Nordio F, Bonventre JV, Xiong L, Zapol WM. Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery. Am J Respir Crit Care Med. 2018 Nov 15;198(10):1279-1287. doi: 10.1164/rccm.201710-2150OC.

    PubMed 29932345

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing inhaled nitric oxide and inhaled Nitrogen in people with Heart Valve Diseases and Heart; Complications, Valve, Prosthesis, run by Xijing Hospital at 1 site in China.

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 4 inclusion and 7 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 Feb 2018. 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 China. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

acute kidney injury (time frame: an increase of serum creatinine by 50% within 7 days after surgery, or an increase of serum creatinine by 0.3 mg/dl within 2 days after surgery). 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 NCT01802619, which also lists 2 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 Feb 2018.

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