Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass

NCT03331146 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: 1709284471
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this study is to evaluate the efficacy of intravenous sodium nitrite compared with placebo in reducing the occurrence of CSA-AK as diagnosed by KDIGO criteria during the first 72 hrs after cardiac surgery in high-risk patients undergoing cardiac surgery. Secondary objectives are to determine whether IV sodium nitrite achieves adequate pharmacokinetics (PK) in patients undergoing cardiac surgery with the use of CPB.

Conditions

Acute Kidney Injury

Keywords

Nitric Oxide; Sodium Nitrite; Cardiopulmonary bypass; cardioplegic cardiac arrest; coronary revacularization

Outcome Measures

Primary Outcomes (4)

• Nitrite Metabolome Levels

  Measuring nitrite, nitrate, and nitrosothiols levels

  baseline to 73 hrs post-operatively

• Biomarkers of Hemolysis

  Measuring hemolysis indicators heme, Hb, hemopexin, and hemopectin

  baseline to 73 hrs post-operatively

• Biomarkers of Kidney Injury

  Measuring kidney injury indicators creatine, neutrophil-associated gelatinase, lipocalin (NGAL)

  baseline to 73 hrs post-operatively

• Cell Cycle Stress

  Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7

  baseline to 73 hrs post-operatively

Secondary Outcomes (6)

• Biomarkers of Hepatic injury

  baseline to 24 hours post-operatively

• Biomarkers of Kidney Injury

  baseline to 24 hours post-operatively

• Cell Cycle Stress

  baseline to 24 hours post-operatively

• Biomarkers of Myocardial Injury

  baseline to 24 hours post-operatively

• Urine Output

  baseline to 73 hrs post-operatively

Study Arms (2)

Control group

PLACEBO COMPARATOR

saline infusion will be administered after induction of general anesthesia

Drug: Saline; Drug: Sodium Nitrite

Sodium Nitrite

ACTIVE COMPARATOR

sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs.

Drug: Saline; Drug: Sodium Nitrite

Interventions

Saline DRUG

A placebo (saline infusion) will be administered after induction of general anesthesia.

Control group; Sodium Nitrite

Sodium Nitrite DRUG

Sodium nitrite infusion at a 267 mcg/kg/hr. will start after induction of general anesthesia via a dedicated IV line for 6 hrs.

Also known as: NaNO2

Control group; Sodium Nitrite

Eligibility Criteria

• Age: 19 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients CCFS score ≥ 6 (Table 1)
• Patients admitted to UAB cardiac intensive care unit (CICU) following elective cardiac surgery with cardiopulmonary bypass under general endotracheal anesthesia
• years old
• Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2

You may not qualify if:

• Prisoners directly admitted from a correctional facility.
• Children \< 19 years or under 50 kg body weight if age is unknown.
• Patients enrolled in a concurrent ongoing interventional, randomized clinical trial.
• Patients with end stage renal disease or preexisting GFR \<30 mL/min/1.73 m2 or need for dialysis. 34
• Patients with end stage heart disease on the cardiac transplant list.
• Patients undergoing procedures without the use of CPB
• All transplant patients.
• Patients on ventricular assist devices.
• Patients undergoing emergency procedures.
• Patients with glucose 6-dehydrogenase deficiency
• Pregnancy

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

UAB Department of Anesthesiology and Perioperative Medicine

Birmingham, Alabama, 35249, United States

Location

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Sodium Chloride; Sodium Nitrite

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Nitrites; Nitrous Acid; Nitrogen Compounds

Study Officials

• Ahmed F Zaky, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 20, 2017
• First Posted: November 6, 2017
• Study Start: October 1, 2018
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2020
• Last Updated: September 27, 2018

Record last verified: 2018-09

Locations

US (1)