Use of Inhaled Nitric Oxide to Prevent Pulmonary Hypertension Associated to Stored Blood Transfusion

Pulmonary Hemodynamic Effects of Stored Red Blood Cell Transfusion in Post-Operative Cardiac Surgical Patients: Influence of Breathing Nitric Oxide. A Randomized Controlled Trial in the Cardiac-Intensive Care Unit.

The objective of this study is to assess if prolonged storage time of a packed red blood cell unit may cause pulmonary vasoconstriction after transfusion, in a susceptible population such as cardiac surgery patients. The investigators will also evaluate the potential reversal effect of Inhaled Nitric Oxide on pulmonary vasoconstriction induced by stored blood transfusions.

Study Overview

• Status: Withdrawn
• Conditions: Hypertension, Pulmonary; Hemolysis
• Intervention / Treatment: Drug: Nitric Oxide

Detailed Description

Patients will be randomized into one of the three groups:

I. Blood transfusion stored for less than 10 days II. Blood transfusion stored for more than 30 days III. Blood transfusion stored for more than 30 days days plus inhalation of Nitric Oxide at 80 part per million for an hour during blood transfusion.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provide written informed consent
2. Elective cardiac or aortic surgery
3. One or more blood transfusions scheduled for clinical reasons
4. Presence of an arterial catheter and pulmonary arterial catheter

Exclusion Criteria:

1. Emergent cardiac surgery.
2. Patients requiring irradiated or washed blood transfusions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Young blood transfusion; The first group of patients (n=30) will be randomized to receive leukoreduced blood transfusion stored for less than 10 days
No Intervention: Old blood transfusion; This randomized group of patients (n=30) will receive leukoreduced blood transfusion stored for more than 30 days
Active Comparator: Old blood transfusion and Nitric Oxide; This randomized group of patients (n=30) will receive leukoreduced blood transfusion stored for more than 30 days while breathing nitric oxide (80 part per million) and oxygen	Drug: Nitric Oxide; Nitric oxide at 80 part per million will be administrated by inhalation for approximately 1 hour during the blood transfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary vascular resistance index	Parameters to calculate pulmonary vascular resistance index will be measured during and after blood transfusion for about 6 hours. The following parameters will be recorded: height, weight, systemic pressure, pulmonary pressure, wedge pressure, central venous pressure, cardiac output) of each subjects will be recorded.	During and after blood transfusion- average time of observation 6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemolysis	Hemolytic markers will be measured such as: haptoglobin, plasma free hemoglobin, hemopexin, and iron metabolites.	During and after blood transfusion- average time of observation 6 hours
Nitric oxide metabolites	Plasma nitric oxide consumption, plasma and red blood cell levels of circulating nitrate, nitrite, nitric will be measured	During and after blood transfusion- average time of observation 6 hours
Inflammation	Inflammation will be assessed by changes of the plasma concentration of cytokines, such as IL-6, IL-8, IL-10, IL-12, TNF, IFN-γ	During and after blood transfusion- average time of observation 6 hours

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Publications and helpful links

General Publications

• Berra L, Pinciroli R, Stowell CP, Wang L, Yu B, Fernandez BO, Feelisch M, Mietto C, Hod EA, Chipman D, Scherrer-Crosbie M, Bloch KD, Zapol WM. Autologous transfusion of stored red blood cells increases pulmonary artery pressure. Am J Respir Crit Care Med. 2014 Oct 1;190(7):800-7. doi: 10.1164/rccm.201405-0850OC.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: August 13, 2014
• First Submitted That Met QC Criteria: August 14, 2014
• First Posted (Estimate): August 15, 2014

Study Record Updates

• Last Update Posted (Estimate): March 18, 2016
• Last Update Submitted That Met QC Criteria: March 16, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Blood Transfusion; Nitric Oxide; Cardiac Surgical Procedures; Catheterization, Swan-Ganz
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Hemolysis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: BloodiNO