A Phase II, Randomized, Placebo-Controlled Trial of Regadenoson in Sickle Cell Anemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 12
- 主要终点
- Number of Participants With a Reduction in Invariant Natural-Killer T-Cell (iNKT Cell) Activation by 70% or More
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 10 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Regadenoson Arm
1.44 mcg/kg/hour infused over 48 hours
干预措施: Regadenoson (Drug)
Placebo Arm
Placebo infused over 48 hours
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With a Reduction in Invariant Natural-Killer T-Cell (iNKT Cell) Activation by 70% or More
时间窗: Baseline-End of study infusion over 48 hours
To determine if infusional Regadenoson reduced iNKT cell activation among individuals with sickle cell anemia (SCA) and pain or acute chest syndrome (ACS) compared to placebo by 70% or greater.
次要结局
- Level of Inflammatory Markers (A2A)(Baseline-End of study infusion over 48 hours)
- Number of Participants With an Improvement in Respiratory Symptoms(Baseline-End of study infusion over 48 hours)
- Opioid Use(Baseline-End of study infusion over 48 hours)
- Length of Hospital Stay(Hospital Presentation- Hospital Discharge, assessed up to 1 month)
- Level of Inflammatory Markers (IL-4)(Baseline-End of study infusion over 48 hours)
- Level of Inflammatory Markers (IFN-gamma)(Baseline-End of study infusion over 48 hours)
研究者
David G. Nathan, MD
Principal Investigator
Dana-Farber Cancer Institute