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

NCT01802619 | Completed Phase 1 DMC

• 2 other identifiers: 20121025-881000232
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 1

Brief 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 plasma-Hb induced NO scavenging.

Conditions

Heart; Complications, Valve, Prosthesis; Heart Valve Diseases; Cardiac Valve Replacement Complication

Outcome Measures

Primary Outcomes (1)

• acute kidney injury

  acute kidney injury was defined by the KDIGO criteria

  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)

• Chronic kidney disease

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

• Loss of 25% of eGFR compared to baseline

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

• Major adverse kidney events (MAKE)

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

• Renal Replacement Therapy

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

• Incidence of nonfatal stroke and nonfatal myocardial infarction.

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

Other Outcomes (3)

• In-hospital stay

  Normally within 30 days, when patients was discharged from ICU

• ICU-stay

  Normally within 30 days, when patients was discharged from ICU

• Incidence of prolonged ventilation

  During hospital stay, normally within 30 days

Study Arms (2)

inhaled nitrogen

PLACEBO COMPARATOR

Using 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.

Other: inhaled Nitrogen

inhaled nitric oxide

EXPERIMENTAL

Using 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.

Other: inhaled nitric oxide

Interventions

inhaled nitric oxide OTHER

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 nitric oxide

inhaled Nitrogen OTHER

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.

inhaled nitrogen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (1)

Xijing Hospital

Xi'an, Shaanxi, 710032, China

Location

Related Publications (2)

• 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.

  PMID: 33481401 DERIVED

• 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.

  PMID: 29932345 DERIVED

MeSH Terms

Conditions

Heart Valve Diseases

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• lize Xiong, M.D.,Ph.D.

  Xijing Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.& Ph.D.

Study Record Dates

• First Submitted: February 25, 2013
• First Posted: March 1, 2013
• Study Start: August 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2016
• Last Updated: February 13, 2018

Record last verified: 2018-02

Locations

CN (1)