AzTrials
AzTrials

Coronary Artery DiseaseNCT02771808

Haptoglobin Polymorphism as a Determinant of Adverse Outcome After Cardiac Surgery in Diabetic Patients

An observational study of Coronary Artery Disease, run by University of Virginia at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Specific aim 1a will test the hypothesis that diabetic patients with 2-2 haptoglobin genotype have higher indices of postoperative myocardial injury (creatine kinase MB isoenzyme , Troponin I ) and renal injury (as indicated by elevated creatinine, cytostatin C and glomerular filtration rate). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Coronary Artery Disease
What is being tested?
biomarker samples
How many people
83 participants
Where
1 siteUnited States
Study dates
Sep 2010to May 2015
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Adult diabetic patients scheduled for an elective cardiac surgery on pump at UVA

Who may be able to join

  • 18 years of age and older
  • Scheduled for an elective cardiac surgery on pump
  • Diabetic -type I or type II
  • Informed consent

Who cannot join

  • Patients with chronic hemolytic disorders;
  • Patients with hemoglobinopathies
  • Enrollment in another interventional clinical trial

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Virginia Health System

    Charlottesville, Virginia, 22908

Other trials in United States

About this study

Specific aim 1a will test the hypothesis that diabetic patients with 2-2 haptoglobin genotype have higher indices of postoperative myocardial injury (creatine kinase MB isoenzyme , Troponin I ) and renal injury (as indicated by elevated creatinine, cytostatin C and glomerular filtration rate). Of note, significantly elevated levels (>5 times the upper normal limit) of creatine kinase MB isoenzyme and troponins postoperatively have been associated with postoperative myocardial ischemia/infarction and are a predictor of short-term and long-term mortality after cardiac surgery.

Specific aim 1b will evaluate preoperative and postoperative indices of oxidative stress (such as isoprostane f2 alpha and malondialdehyde) and will evaluate whether patients with type 2-2 haptoglobin express increased oxidative stress. The investigators will also try to correlate whether patients with increased oxidative stress are those with elevated indices of myocardial and/or renal injury Specific aim 1c will try to evaluate whether patients with type 2-2 haptoglobin also have increased levels of inflammatory indices (C-reactive protein,[interleukin] IL-1, IL-2, IL-6, TNF[tumor necrosis factor]) and try to correlate the findings with postoperative myocardial and or renal injury.

The incidence of atrial fibrillation after coronary artery bypass graft ranges from 19% to 27%. The investigators will also look at any correlation of the type 2-2 haptoglobin and the incidence of post-operative atrial fibrillation.

Read the detailed description

Diabetes mellitus is a major risk factor for postoperative morbidity and mortality after cardiac surgery, mainly because of accelerated atherosclerosis and target-organ injury that predispose these patients to increased incidence of postoperative morbidity (such as but not limited to, postoperative adverse cardiac events, renal injury or stroke) and mortality.

Over the past several years haptoglobin has been identified as a risk factor that predicts the development of cardiovascular complications in diabetics. There are 3 major haplotypes of haptoglobin: 1-1; 1-2 and 2-2. Several studies have demonstrated that diabetic individuals with the 2-2 genotype have up to 5 fold increased risk to develop cardiovascular complications as compared to diabetic patients with a non-2-2 haptoglobin genotype. There is no data in the literature that evaluated whether the haptoglobin 2-2 genotype is a risk factor for increased postoperative morbidity and/or mortality after cardiac surgery in patients with DM.

Therefore, the aims of the study are to evaluate whether diabetic patients with the 2-2 genotype are at increased risk for postoperative morbidity and/or mortality after cardiac surgery.

Preliminary studies in diabetic patients demonstrated that those with haptoglobin 2-2 genotype are at increased risk for cardiovascular complications of diabetes. Moreover, these patients were found to have increased in-hospital mortality after acute MI compared to diabetic individuals that do not have the 2-2 genotype, and they also suffer from increased incidence of post catheterization stent thrombosis compared to diabetics that do not have the 2-2 genotype

Being tested
biomarker samples
Keywords
CABG
Medical subject headings
Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • biomarker samplesOther

    Also called haptoglobin

    biomarker samples for haptoglobin genotype (RT-PCR) and phenotype (hemoglobin electrophoresis) general markers for oxidative stress (isoprostane f2 alpha, malondialdehyde) markers of inflammation (CRP, IL-1, 2, 6, 10 and TNF) markers of cardiac injury (CPK, troponins and BNP) markers of kidney injury (cystatin C, creatinine, GFR)

Study groups in NCT02771808
Study groupRoleWhat they receive
diabetic patientsobtain biomarker samples from diabetic patients and examine for 1-1 \& 1-2 \& 2-2 haptoglobin genotype
Receives: Other: biomarker samples

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. number of participants with myocardial injury

    number of participants with general markers for myocardial injury

    Measured: 24 hours post CPB

Secondary outcomes (2)
  1. number of participants with renal injury

    number of participants with markers of kidney injury (cystatin C, creatinine, GFR)

    Measured: 24 hrs post CPB

  2. number of participants with incidence of new onset atrial fibrillation

    incidence of new onset atrial fibrillation will be recorded

    Measured: day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2016 (estimated)
  2. Study startSep 2010
  3. Primary completionMay 2015
  4. Study completionMay 2015

Resources

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
Case only
Time perspective
Prospective
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02771808
Sponsor's protocol ID
14691
Status last verified
May 2016
First submitted
17 Sep 2010
Last updated
13 May 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Moreno PR, Fuster V. New aspects in the pathogenesis of diabetic atherothrombosis. J Am Coll Cardiol. 2004 Dec 21;44(12):2293-300. doi: 10.1016/j.jacc.2004.07.060.

    PubMed 15607389
  • Donahoe SM, Stewart GC, McCabe CH, Mohanavelu S, Murphy SA, Cannon CP, Antman EM. Diabetes and mortality following acute coronary syndromes. JAMA. 2007 Aug 15;298(7):765-75. doi: 10.1001/jama.298.7.765.

    PubMed 17699010
  • Bucerius J, Gummert JF, Walther T, Doll N, Falk V, Onnasch JF, Barten MJ, Mohr FW. Impact of diabetes mellitus on cardiac surgery outcome. Thorac Cardiovasc Surg. 2003 Feb;51(1):11-6. doi: 10.1055/s-2003-37280.

    PubMed 12587082
  • Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH. Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery. J Am Coll Cardiol. 2002 Aug 7;40(3):418-23. doi: 10.1016/s0735-1097(02)01969-1.

    PubMed 12142105
  • Thourani VH, Weintraub WS, Stein B, Gebhart SS, Craver JM, Jones EL, Guyton RA. Influence of diabetes mellitus on early and late outcome after coronary artery bypass grafting. Ann Thorac Surg. 1999 Apr;67(4):1045-52. doi: 10.1016/s0003-4975(99)00143-5.

    PubMed 10320249
  • Levy AP, Hochberg I, Jablonski K, Resnick HE, Lee ET, Best L, Howard BV; Strong Heart Study. Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Cardiol. 2002 Dec 4;40(11):1984-90. doi: 10.1016/s0735-1097(02)02534-2.

    PubMed 12475459
  • Roguin A, Koch W, Kastrati A, Aronson D, Schomig A, Levy AP. Haptoglobin genotype is predictive of major adverse cardiac events in the 1-year period after percutaneous transluminal coronary angioplasty in individuals with diabetes. Diabetes Care. 2003 Sep;26(9):2628-31. doi: 10.2337/diacare.26.9.2628.

    PubMed 12941730
  • Suleiman M, Aronson D, Asleh R, Kapeliovich MR, Roguin A, Meisel SR, Shochat M, Sulieman A, Reisner SA, Markiewicz W, Hammerman H, Lotan R, Levy NS, Levy AP. Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction. Diabetes. 2005 Sep;54(9):2802-6. doi: 10.2337/diabetes.54.9.2802.

    PubMed 16123372
  • Asleh R, Guetta J, Kalet-Litman S, Miller-Lotan R, Levy AP. Haptoglobin genotype- and diabetes-dependent differences in iron-mediated oxidative stress in vitro and in vivo. Circ Res. 2005 Mar 4;96(4):435-41. doi: 10.1161/01.RES.0000156653.05853.b9. Epub 2005 Jan 20.

    PubMed 15662028
  • Guetta J, Strauss M, Levy NS, Fahoum L, Levy AP. Haptoglobin genotype modulates the balance of Th1/Th2 cytokines produced by macrophages exposed to free hemoglobin. Atherosclerosis. 2007 Mar;191(1):48-53. doi: 10.1016/j.atherosclerosis.2006.04.032. Epub 2006 Jul 3.

    PubMed 16820150
  • Greenson N, Macoviak J, Krishnaswamy P, Morrisey R, James C, Clopton P, Fitzgerald R, Maisel AS. Usefulness of cardiac troponin I in patients undergoing open heart surgery. Am Heart J. 2001 Mar;141(3):447-55. doi: 10.1067/mhj.2001.113071.

    PubMed 11231444
  • Muehlschlegel JD, Perry TE, Liu KY, Nascimben L, Fox AA, Collard CD, Avery EG, Aranki SF, D'Ambra MN, Shernan SK, Body SC; CABG Genomics Investigators. Troponin is superior to electrocardiogram and creatinine kinase MB for predicting clinically significant myocardial injury after coronary artery bypass grafting. Eur Heart J. 2009 Jul;30(13):1574-83. doi: 10.1093/eurheartj/ehp134. Epub 2009 Apr 30.

    PubMed 19406870
  • Paparella D, Cappabianca G, Visicchio G, Galeone A, Marzovillo A, Gallo N, Memmola C, Schinosa Lde L. Cardiac troponin I release after coronary artery bypass grafting operation: effects on operative and midterm survival. Ann Thorac Surg. 2005 Nov;80(5):1758-64. doi: 10.1016/j.athoracsur.2005.04.040.

    PubMed 16242452
  • Ramsay J, Shernan S, Fitch J, Finnegan P, Todaro T, Filloon T, Nussmeier NA. Increased creatine kinase MB level predicts postoperative mortality after cardiac surgery independent of new Q waves. J Thorac Cardiovasc Surg. 2005 Feb;129(2):300-6. doi: 10.1016/j.jtcvs.2004.06.005.

    PubMed 15678039
  • Adabag AS, Rector T, Mithani S, Harmala J, Ward HB, Kelly RF, Nguyen JT, McFalls EO, Bloomfield HE. Prognostic significance of elevated cardiac troponin I after heart surgery. Ann Thorac Surg. 2007 May;83(5):1744-50. doi: 10.1016/j.athoracsur.2006.12.049.

    PubMed 17462392

Questions about this trial

What is this clinical trial studying?

An observational study of Coronary Artery Disease, run by University of Virginia at 1 site in United States.

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 4 inclusion and 3 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 13 May 2016. 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 United States. 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?

number of participants with myocardial injury (time frame: 24 hours post CPB). 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 NCT02771808, which also lists 23 linked publications.

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 13 May 2016; AzTrials last refreshed its copy on 7 Nov 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in