A Phase II Trial of Regadenoson in Sickle Cell Anemia
Condition: Sickle Cell Anemia
MeSH terms: Anemia; Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      If you are willing to participate in this research study you will be asked to undergo some
      screening tests and procedures to confirm your eligibility. Many of these tests and
      procedures are likely to be part of regular sickle cell anemia care and may be done even if
      it turns out that you do not take part in the research study. If you have had some of these
      tests and procedures recently, they may or may not have to be repeated. The tests and
      procedures include: a medical history, physical examination, blood tests, blood or urine
      pregnancy test (if applicable) and an electrocardiogram. If these tests show that you are
      eligible to participate in the research study, you will begin the study treatment. If you do
      not meet the eligibility criteria, you will not be able to participate in the research study.
      At the time of screening we will also ask you about your pain level.

      Because no one knows which of the study options is best, you will be "randomized" into one of
      the study groups: the "study drug" group, which will receive Regadenoson, or the "control"
      group, which will receive placebo. Randomization means that you are put into a group by
      chance. It is like flipping a coin. Neither you nor the research doctor will choose what
      group you will be in. You will have an equal (50/50) chance of being placed in either group.
      Neither you nor the research doctor will know what group you are in.

      You will be given a study medication and it will contain either Regadenoson or placebo
      (fluids with no medicine).

      You will be given one infusion of the study drug while you are admitted to the hospital for a
      pain crisis. The study drug will be infused with fluids. You will stay in the hospital for at
      least 3 days and 2 nights. Your infusion will be 48 hours long, followed by a 6-hour
      observation period. During your infusion, you will receive standard treatment for your pain
      crisis. The study drug will be given through a separate part of your body from the infusions
      that are part of your standard treatment. The study drug will not be available after your
      participation in the study ends.

      Before the infusion: We will place a small tube in your vein called an IV, which will be used
      only to infuse the study drug. It will not be used for infusions that are part of standard
      treatment for your pain crisis. During the study drug infusion, standard treatment will be
      given through a separate IV. We can use your standard treatment IV or a needle to draw blood
      for the required blood test. If it is hard to draw blood from your veins, we may ask you if
      you would like to use a peripherally inserted central catheter (PICC line) for your blood
      draws. A PICC line is a small tube that is placed in a vein in your arm and goes through to a
      vein in your chest. A chest x-ray is usually done to make sure it is in the right veins. It
      is your choice to decide whether you would like to use a PICC line. We will record your blood
      pressure and heart rate every 5-10 minutes, until they have stabilized. We will also ask you
      about your pain level at the time of your blood test.

      During the 48 hour infusion: Your heart rate and the amount of oxygen in your blood will be
      monitored continuously using a device that fits over your finger. We will take about 2-3
      teaspoons of blood at 24 and 48 hours after the beginning of your infusion for tests to try
      to understand how the drug affects your body. We will ask you about your pain level at the
      time of each blood test. We will take your blood pressure every 30 minutes for the first 2
      hours, then every hour for the next two hours, then every 2 hours for the remainder of the
      infusion.

      A six hour observation period will take place immediately after the infusion. At this time
      you will undergo the following: your heart rate and the amount of oxygen in your blood will
      be monitored continuously with a device that fits over your finger. We will take about 5
      teaspoons of blood at the end of the period to try to understand how the study drug affects
      your body. We will ask you about your pain level at the time of your blood test. We will take
      your blood pressure every 2 hours for the full duration of the observation period.

      You may not eat or drink anything that contains caffeine, such as coffee, tea, chocolate or
      sodas during the infusion and observation periods.

      We would like to keep track of your medical condition for 30 days after you receive the study
      drug. We would like to do this by contacting you on the telephone weekly during the 30 days
      after your participation to see how you are doing.
    

Intervention name(s): Regadenoson; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Other intervention name(s): Lexiscan; Regadenoson Placebo, Lexiscan Placebo, 0.9% Normal Saline
Intervention MeSH terms: Regadenoson
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment