Other Functional Disturbances Following Cardiac SurgeryNCT01883713
Study of Methemoglobin as a Biomarker of Tissue Hypoxia During Acute Hemodilution in Heart Surgery Patients
An observational study of Other Functional Disturbances Following Cardiac Surgery, run by Unity Health Toronto at 1 site in Canada.
Trial summary
Acute and chronic anemia continue to be associated with increased mortality in a number of clinical settings, including cardiac and non-cardiac surgery. However, "We have no clinical measures that let us know of impending insufficient oxygenation as anemia progresses" (R.B. Weiskopf). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Other Functional Disturbances Following Cardiac Surgery
- What is being tested?
- Brain Oximetry
- Type of treatment
- Medical device
- How many people
- 68 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2013to Aug 2016
- Phase
- Observational
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: heart surgery with cardiopulmonary bypass
Who may be able to join
- patients undergoing heart surgery using cardiopulmonary bypass at St. Michael's Hospital who have a pre-operative Hb value greater than 90 g/L, no evidence of hypoxemia (SaO2 > 90%) and no history of congenital methemoglobinemia.
Who cannot join
- severe hypoxemia, acute or chronic renal failure requiring dialysis, emergency surgery or the lack of a PA catheter (current standard of care at St. Michael's Hospital is to insert a PA catheter in > 90% of patients).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Analysis of Methemoglobin as a Biomarker of Tissue Hypoxia During Acute Hemodilutional Anemia in Patients Undergoing Heart Surgery
Acute and chronic anemia continue to be associated with increased mortality in a number of clinical settings, including cardiac and non-cardiac surgery. However, "We have no clinical measures that let us know of impending insufficient oxygenation as anemia progresses" (R.B. Weiskopf). The current proposal is based on experimental and clinical data which suggest that plasma methemoglobin (MetHb) may be a sensitive biomarker of tissue hypoxia and "anemic stress" in surgical patients.
Hypothesis: Increased methemoglobin is a biomarker of tissue hypoxia during acute anemia.
Primary Objective: To demonstrate a direct relationship between decreased Hb and increased MetHb in patients undergoing acute hemodilution on cardiopulmonary bypass (CPB).
Read the detailed description
Acute and chronic anemia continue to be associated with increased mortality in a number of clinical settings, including cardiac and non-cardiac surgery. 1-6 However, as recently stated by one of the pioneers of anemia research; Dr. R.B. Weiskopf: "We have no clinical measures that let us know of impending insufficient oxygenation as anemia progresses".7 Toward achieving this goal, we have developed experimental models to define the adaptive mechanisms which maintain oxygen homeostasis during acute anemia. Our research has identified that increased nitric oxide (NO) production by nitric oxide syntheses (NOSs) may be an important survival mechanism in acute anemia.3;8;9 Experimental data suggests that nNOS may promote survival by maintaining oxygen (O2) homeostasis during acute anemia.10 Resultant increases in nitric oxide (NO) contributes to adaptive cell signaling mechanisms and also increase oxidation of hemoglobin (Hb) to methemoglobin (MetHb).3 In addition, oxygen extraction results in increased levels of deoxyhemoglobin which has been proposed to act as a nitrite (NO2-) reductase to generate additional bioactive NO, thereby promoting vasodilation in hypoxic vascular beds.11-15 Thus, by more than one mechanism, increased MetHb may be indicative of hemoglobin desaturation, tissue hypoxia and activation of adaptive tissue responses to anemia. These responses may identify the threshold for local tissue hypoxia or "anemic stress". In attempt to determine if such mechanisms are active in humans we performed a retrospective study in patients undergoing cardiopulmonary bypass (CPB) during heart surgery to determine if plasma MetHb increased as Hb decreased during CPB. We observed an inverse relationship between Hb and MetHb that was independent of red blood cell transfusion and exogenous nitrate use
- Being tested
- Brain Oximetry
- Keywords
- anemia, CPB, methemoglobin, hypoxia
- Medical subject headings
- Anemia, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brain OximetryDevice
Also called Nonin equinox oximeter
Non invasive brain oximeter will be applied on the patient's forehead to monitor the brain oxygen saturation throughout the surgery.
| Study group | Role | What they receive |
|---|---|---|
| Heart surgery during CPB | All patients undergoing heart surgery using cardiopulmonary bypass who have a pre-operative Hb value greater than 90 g/L, no evidence of hypoxemia (SaO2 > 90%) and no history of congenital methemoglobinemia. Exclusion criteria will include severe hypoxemia, acute or chronic renal failure requiring dialysis, emergency surgery or the lack of a PA catheter. Non invasive brain oximetry will be used to assess the brain oxygen tension during surgical procedure. Receives: Device: Brain Oximetry |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arterial methemoglobin levels
To determine if there is an association between increased methemoglobin and tissue hypoxia following heart surgery
Measured: 18 months
Secondary outcomes (4)
Cerebral tissue oxygen saturation
Measured: 18 months
Plasma erythropoietin levels
Measured: 18 months
Plasma nitrate/nitrite levels
Measured: 18 months
Plasma hepcidin levels
Relationship between plasma hepcidin levels and hemoglobin levels
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2013 (estimated)
- Study startJan 2013
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Other Functional Disturbances Following Cardiac SurgeryStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gregory Hare, MD, PhD, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01883713
- Sponsor's protocol ID
- REB# 12-015
- Status last verified
- Apr 2018
- First submitted
- 11 Mar 2013
- Last updated
- 17 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hare GMT, Han K, Leshchyshyn Y, Mistry N, Kei T, Dai SY, Tsui AKY, Pirani RA, Honavar J, Patel RP, Yagnik S, Welker SL, Tam T, Romaschin A, Connelly PW, Beattie WS, Mazer CD. Potential biomarkers of tissue hypoxia during acute hemodilutional anemia in cardiac surgery: A prospective study to assess tissue hypoxia as a mechanism of organ injury. Can J Anaesth. 2018 Aug;65(8):901-913. doi: 10.1007/s12630-018-1140-0. Epub 2018 Apr 25.
PubMed 29696581
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Analysis of Methemoglobin as a Biomarker of Tissue Hypoxia During Acute Hemodilutional Anemia in Patients Undergoing Heart Surgery
- ClinicalTrials.gov ID
- NCT01883713
- Acronym / sponsor ID
- REB# 12-015
- Keywords
- anemia, CPB, methemoglobin, hypoxia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 21 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute and chronic anemia continue to be associated with increased mortality in a number of clinical settings, including cardiac and non-cardiac surgery. However, "We have no clinical measures that let us know of impending insufficient oxygenation as anemia progresses" (R.B. Weiskopf). The current proposal is based on experimental and clinical data which suggest that plasma methemoglobin (MetHb) may be a sensitive biomarker of tissue hypoxia and "anemic stress" in surgical patients.
Hypothesis: Increased methemoglobin is a biomarker of tissue hypoxia during acute anemia.
Primary Objective: To demonstrate a direct relationship between decreased Hb and increased MetHb in patients undergoing acute hemodilution on cardiopulmonary bypass (CPB).
Detailed description
Acute and chronic anemia continue to be associated with increased mortality in a number of clinical settings, including cardiac and non-cardiac surgery. 1-6 However, as recently stated by one of the pioneers of anemia research; Dr. R.B. Weiskopf: "We have no clinical measures that let us know of impending insufficient oxygenation as anemia progresses".7 Toward achieving this goal, we have developed experimental models to define the adaptive mechanisms which maintain oxygen homeostasis during acute anemia. Our research has identified that increased nitric oxide (NO) production by nitric oxide syntheses (NOSs) may be an important survival mechanism in acute anemia.3;8;9 Experimental data suggests that nNOS may promote survival by maintaining oxygen (O2) homeostasis during acute anemia.10 Resultant increases in nitric oxide (NO) contributes to adaptive cell signaling mechanisms and also increase oxidation of hemoglobin (Hb) to methemoglobin (MetHb).3 In addition, oxygen extraction results in increased levels of deoxyhemoglobin which has been proposed to act as a nitrite (NO2-) reductase to generate additional bioactive NO, thereby promoting vasodilation in hypoxic vascular beds.11-15 Thus, by more than one mechanism, increased MetHb may be indicative of hemoglobin desaturation, tissue hypoxia and activation of adaptive tissue responses to anemia. These responses may identify the threshold for local tissue hypoxia or "anemic stress". In attempt to determine if such mechanisms are active in humans we performed a retrospective study in patients undergoing cardiopulmonary bypass (CPB) during heart surgery to determine if plasma MetHb increased as Hb decreased during CPB. We observed an inverse relationship between Hb and MetHb that was independent of red blood cell transfusion and exogenous nitrate use
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Heart surgery during CPB | – | Device: Brain OximetryAll patients undergoing heart surgery using cardiopulmonary bypass who have a pre-operative Hb value greater than 90 g/L, no evidence of hypoxemia (SaO2 > 90%) and no history of congenital methemoglobinemia. Exclusion criteria will include severe hypoxemia, acute or chronic renal failure requiring dialysis, emergency surgery or the lack of a PA catheter. Non invasive brain oximetry will be used to assess the brain oxygen tension during surgical procedure. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- heart surgery with cardiopulmonary bypass
Key inclusion criteria (1 listed)
- patients undergoing heart surgery using cardiopulmonary bypass at St. Michael's Hospital who have a pre-operative Hb value greater than 90 g/L, no evidence of hypoxemia (SaO2 > 90%) and no history of congenital methemoglobinemia.
Key exclusion criteria (1 listed)
- severe hypoxemia, acute or chronic renal failure requiring dialysis, emergency surgery or the lack of a PA catheter (current standard of care at St. Michael's Hospital is to insert a PA catheter in > 90% of patients).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Brain OximetryAlso: Nonin equinox oximeterNon invasive brain oximeter will be applied on the patient's forehead to monitor the brain oxygen saturation throughout the surgery. | Device | Heart surgery during CPB |
Primary outcome
Arterial methemoglobin levels
Time frame: 18 months
To determine if there is an association between increased methemoglobin and tissue hypoxia following heart surgery
4 secondary outcomes
Cerebral tissue oxygen saturation
Time frame: 18 months
Plasma erythropoietin levels
Time frame: 18 months
Plasma nitrate/nitrite levels
Time frame: 18 months
Plasma hepcidin levels
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2018.
- Derived from this study: PubMed 29696581Hare GMT, Han K, Leshchyshyn Y, Mistry N, Kei T, Dai SY, Tsui AKY, Pirani RA, Honavar J, Patel RP, Yagnik S, Welker SL, Tam T, Romaschin A, Connelly PW, Beattie WS, Mazer CD. Potential biomarkers of tissue hypoxia during acute hemodilutional anemia in cardiac surgery: A prospective study to assess tissue hypoxia as a mechanism of organ injury. Can J Anaesth. 2018 Aug;65(8):901-913. doi: 10.1007/s12630-018-1140-0. Epub 2018 Apr 25.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory Hare, MD, PhD principal investigator
Unity Health Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Other Functional Disturbances Following Cardiac Surgery, run by Unity Health Toronto at 1 site in Canada.
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 1 inclusion and 1 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 17 Apr 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Arterial methemoglobin levels (time frame: 18 months). 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 NCT01883713, which also lists 1 linked publication.
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 17 Apr 2018.