A Phase II Trial of Regadenoson in Sickle Cell Anemia
Condition: Sickle Cell Anemia
MeSH terms: Anemia; Anemia, Sickle Cell
Intervention: Regadenoson; Placebo
Intervention description: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.; This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Intervention MeSH terms: Regadenoson
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 100.0
Sex: All
Minimum age: 10 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This research study is a Phase II clinical trial, which tests the safety and effectiveness of
      an investigational drug called Regadenoson (or Lexiscan) to learn whether the drug works in
      treating a specific disease, in this case Sickle Cell Disease (SCD). "Investigational" means
      that the drug is being studied. It also means that the FDA has not yet approved the drug for
      your type of disease.

      SCD is an inherited blood disorder that causes the red blood cells to change their shape from
      a round shape to a half-moon/crescent or sickled shape. People who have SCD have a different
      type of protein that carries oxygen in their blood (hemoglobin) than people without SCD. This
      different type of hemoglobin makes the red blood cells change into crescent shape under
      certain conditions. Sickle-shaped cells are a problem because they often get stuck in the
      blood vessels blocking the flow of blood, and cause inflammation and injury to important
      areas in the body.

      Regadenoson (trade name Lexiscan) is a drug that may prevent this inflammation and injury
      caused by the sickle shaped cells. This drug is approved by the FDA to be used as a fast
      infusion during a heart stress test in people who are unable to exercise enough to put stress
      on their heart by making the heart beat faster. Regadenoson has been studied as a long
      infusion at this dose in adults, and no safety issues have been identified
      (ClinicalTrials.gov Identifier: NCT01085201). This is the first study to look at patient
      benefit with the long infusion of the drug. This drug has been used in laboratory experiments
      and information from those other research studies suggests that this drug may help to protect
      the body from damage caused by sickle-shaped cells in this research study.

      In this research study, the investigators are specifically looking to see if Regadenoson is
      an effective treatment for pain crises and acute chest syndrome in SCD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have sickle cell anemia confirmed by hemoglobin analysis

          -  Must be admitted to hospital for pain or ACS

          -  Reliable IV access as determined by the study physician

          -  Participants must have the laboratory indices as defined below:

               -  Hemoglobin ≥ 5 g/dL

               -  Platelets > 100,000/mcL

               -  ALT (SGPT) < 3 X institutional upper limit of normal

               -  Serum creatinine ≤ 1.5 mg/dL

               -  INR ≤2.0, PTT ≤ 48 seconds

        Exclusion Criteria:

          -  Pregnant or breastfeeding

          -  Current physician diagnosis of asthma defined by treatment with systemic
             corticosteroids within the last 12 months or predicted/current use of asthma
             controller medications

          -  10 or more hospitalizations for pain in the last 12 months

          -  Receiving regularly scheduled transfusions

          -  Severe ACS

          -  Second or third degree AV block or sinus node dysfunction

          -  History of a bleeding diathesis

          -  History of clinically overt stroke within 3 years

          -  History of severe hypertension not adequately controlled with anti-hypertensive
             medications

          -  Receiving chronic anti-coagulation or anti-platelet therapy

          -  History of metastatic cancer

          -  Receiving any other study agents or have received a study agent in the past 30 days

          -  Uncontrolled intercurrent illness

          -  Known HIV

          -  Have previously enrolled and received the investigational agent as part of this study

          -  Taking medications that may interact with the investigational agent

          -  Have previously undergone a hematopoietic stem cell transplant or solid organ
             transplant