The Impact of Age-dependent Haptoglobin Deficiency on Plasma Free Hemoglobin Levels During Extracorporeal Membrane Oxygenation Support

Respiratory Failure Clinical Trial

Official title:

The Impact of Age-dependent Haptoglobin Deficiency on Plasma Free Hemoglobin Levels During Extracorporeal Membrane Oxygenation Support

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03472768
• Other study ID #: 16-2058
• Status: Active, not recruiting
• Start date: September 25, 2018
• Est. completion date: September 2024

Study information

• Verified date: December 2023
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Newborns and children with life-threatening heart and lung failure may require support with ECMO (extracorporeal membrane oxygenation). With ECMO, oxygen and carbon dioxide are exchanged and circulated throughout the body even if the heart is unable to do so. Unfortunately, ECMO can cause breakdown of the red blood cells (known as hemolysis). For unclear reasons, newborns are at particularly high risk of hemolysis while being supported by ECMO. The amount of hemolysis is measured with concentrations of a breakdown product from red blood cells known as free hemoglobin. One possible reason for high free hemoglobin levels in newborns on ECMO could be related to another blood protein called haptoglobin. Haptoglobin is known to help in clearing free hemoglobin through the kidneys into the urine. However, haptoglobin levels in newborns can be very low and increases slowly during the first few months of life. Free hemoglobin may be inappropriately high in newborns supported by ECMO because of low levels of haptoglobin. The purpose of this study is to characterize haptoglobin, free hemoglobin, and hemolysis in newborns and children supported by ECMO and compare those values to age-matched newborns and children not on ECMO.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• ECMO group - Thirty critically-ill children (age newborn to 18 years) who are intubated and supported by ECMO. We will target enrollment of 15 subjects less than 12 months of age (with at least 10 subjects enrolled less than 6 months of age) and 15 subjects over 12 months of age. These targets are set to address the secondary aim in the context of normal adult-level haptoglobin concentrations reportedly achieved by 6-12 months of age.
• Age-matched control group - Sixty critically-ill children (age newborn to 18 years) who are intubated with acute respiratory failure due to any cause and not supported by ECMO. Two control subjects will be enrolled for every 1 experimental ECMO subject.

Age-matching will be performed by the following age groups:

• Neonates 37-40 weeks gestation
• Neonates 40-42 weeks gestation
• Neonates 42-44 weeks gestation
• Neonates 44-46 weeks gestation
• Neonates 46-48 weeks gestation
• Infants 2-4 months of age
• Infants 4-6 months of age
• Infants 6-12 months of age
• Children 1-4 years of age
• Children 4-8 years of age
• Children 8-12 years of age
• Children 12-18 years of age Age-matched control subjects will proceed through the 3 total blood sample collections even if endotracheal extubation occurs within the 3 days of study participation. Age-matching is intended to collect a sample population comparable to the ECMO subject population. We will not match to gender.

Exclusion Criteria (both groups, ECMO and age-matched controls):

• Personal or family history of thrombotic, hemorrhagic, or hemolytic disease.
• Personal history of hematologic malignancy.
• Premature neonates less than 37-weeks gestation and/or less than 2 kg in weight.
• Infection will not be an excluding factor for either subject group.

Related Conditions & MeSH terms

• Respiratory Failure
• Respiratory Insufficiency

Intervention

Diagnostic Test:
• Plasma Haptoglobin Concentration
N/A, comparison of haptoglobin concentration between groups

Locations

Country	Name	City	State
United States	Children's Hospital Colorado and the University of Colorado School of Medicine	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterize the relationship between plasma haptoglobin and free hemoglobin levels in children supported by ECMO.	Serum Haptoglobin (Hp) will be measured daily for 7 days in subjects supported by Extracorporeal Membrane Oxygenation (ECMO). In particular, the relative deficiency of Hp production in neonates will be associated with higher Hp levels. In older children with normal and adequate Hp production, there will be consistently low fHgb concentrations regardless of the other risk factors for hemolysis during ECMO support.	Daily for 7 days
Primary	Characterize the relationship between plasma haptoglobin and free hemoglobin levels in children supported by ECMO.	Plasma free hemoglobin (fHgb) concentrations will be extracted from the medical record. Periods of high fHgb associated with hemolysis during ECMO support will be associated with deficiency of Hp at that time.	7 days
Secondary	Characterize the deficiency of plasma haptoglobin at birth.	Serum Hp and fHgb will be measured daily for 3 days in age-matched control subjects to characterize levels in a cohort of critically-ill children comparable to the ECMO cohort. Neonates and children with non-ECMO supported critical illness will have negligible risk for hemolysis and, thus, low plasma fHgb. Serum Hp concentrations will be similar to the previously-characterized norms in healthy subjects (eg. deficient at birth until 6-12 months of age).	Daily for 3 days