Clinical trial NCT01788631: A Phase II Trial of Regadenoson in Sickle Cell Anemia
Official title: A Phase II, Randomized, Placebo-Controlled Trial of Regadenoson in Sickle Cell Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Anemia
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Boston Children's Hospital
name: La Jolla Institute for Allergy & Immunology
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Washington University School of Medicine
name: Children's Hospital Medical Center, Cincinnati
name: University of Illinois at Chicago
name: Medical College of Wisconsin
name: Duke University
name: Johns Hopkins University
name: Wayne State University
name: Baylor College of Medicine
name: UCSF Benioff Children's Hospital Oakland
First posted: 2013-02-11
Enrollment: 100
Sex: ALL
Minimum age (years): 10
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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

Primary outcomes:
measure: Number of Participants With a Reduction in Invariant Natural-Killer T-Cell (iNKT Cell) Activation by 70% or More
timeFrame: Baseline-End of study infusion over 48 hours
Secondary outcomes:
measure: Length of Hospital Stay
timeFrame: Hospital Presentation- Hospital Discharge, assessed up to 1 month
measure: Number of Participants With an Improvement in Respiratory Symptoms
timeFrame: Baseline-End of study infusion over 48 hours
measure: Opioid Use
timeFrame: Baseline-End of study infusion over 48 hours
measure: Level of Inflammatory Markers (A2A)
timeFrame: Baseline-End of study infusion over 48 hours
measure: Level of Inflammatory Markers (IL-4)
timeFrame: Baseline-End of study infusion over 48 hours
measure: Level of Inflammatory Markers (IFN-gamma)
timeFrame: Baseline-End of study infusion over 48 hours
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Dana-Farber Cancer Institute
name: David Nathan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Field JJ, Majerus E, Gordeuk VR, Gowhari M, Hoppe C, Heeney MM, Achebe M, George A, Chu H, Sheehan B, Puligandla M, Neuberg D, Lin G, Linden J, Nathan DG. Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease. Blood Adv. 2017 Aug 28;1(20):1645-1649. doi: 10.1182/bloodadvances.2017009613. eCollection 2017 Sep 12.