The Erythropoietin NeuroProtective Effect: Assessment in CABG Surgery (TENPEAKS)
Condition: Cardiac Surgery; Brain Injury
MeSH terms: Brain Injuries
Study type: Interventional
Phase: Phase 2

Summary: 
      Context: Neurocognitive dysfunction complicates coronary artery bypass graft surgery.
      Neurocognitive dysfunction is a measurable problem with thinking. Erythropoietin may be a
      neuroprotectant.

      Objective: To investigate the feasibility and safety of three doses of human recombinant
      erythropoietin to reduce neurocognitive dysfunction in coronary artery bypass graft patients.
    

Detailed description: 
      Coronary artery bypass surgery (CABG) is performed each year on over 500,000 patients in the
      US and almost 30,000 patients in Canada to treat coronary artery disease. However, it is
      complicated by a significant postoperative risk of neurologic sequelae, including stroke and
      neurocognitive dysfunction (NCD). Clinically overt stroke, which may be seen in 1-4% of
      patients, is far less common than NCD, which is reported in approximately 50-75% of patients
      at discharge, 20-50% at 6 weeks and up to 40% at five years.Human recombinant erythropoietin
      (rh-Epo) is not only approved in this population for prophylactic use to reduce blood
      transfusions, but has become an agent of intense interest for neuroprotection as a result of
      in vitro data, animal experiments, and now, two promising preliminary trials in human
      patients. There are not, however, any pilot data by which to estimate an appropriate dose or
      treatment effect of rh-Epo on NCD specifically. It is imperative both to refine estimates of
      control group incidence rates, treatment effect and test variability in CABG, as well to
      demonstrate the feasibility and safety of a study protocol, prior to embarking on a larger
      randomized controlled trial powered with an adequate sample size to investigate the efficacy
      of rh-Epo in the reduction of peri-operative NCD. We propose a six month prospective study in
      CABG patients to investigate the feasibility and safety of three prophylactic doses of human
      recombinant erythropoietin (rh-Epo) in a randomized, placebo controlled study. The four study
      arms are: placebo, 375 U/kg, 750 U/kg, or 1500 U/kg of human recombinant erythropoietin
      intravenously divided in three doses, the day before, the day of and the day after surgery.
      The primary outcomes of this pilot will be study feasibility and patient safety as measured
      by ICU and Hospital length of stay, 28 day all cause mortality, and incidence of morbidity
      including pure red cell aplasia (PRCA), stroke, myocardial infarction, re-operation, deep
      vein thrombosis, and pulmonary thromboembolism. The secondary outcome will be the incidence
      of neurocognitive dysfunction among the four study arms and between placebo and rh-Epo at any
      dose. As well, little is known about the pharmacology of rh-Epo in crossing the blood-brain
      barrier. In those patients receiving a spinal anesthetic in addition to a general anesthetic
      as part of their normal care, CSF will be analyzed for rh-Epo concentration, and then
      compared to drug dose and serum level.
    

Intervention name(s): Human recombinant erythropoietin
Intervention type(s): Drug
Intervention MeSH terms: Epoetin Alfa
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Cardiac bypass surgery