A Phase II Trial of Regadenoson in Sickle Cell Anemia

NCT01788631 | Completed Phase 2 Results DMC

• 2 other identifiers: 13-0051P50HL110790-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 12

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.

Conditions

Sickle Cell Anemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Reduction in Invariant Natural-Killer T-Cell (iNKT Cell) Activation by 70% or More

  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.

  Baseline-End of study infusion over 48 hours

Secondary Outcomes (6)

• Length of Hospital Stay

  Hospital Presentation- Hospital Discharge, assessed up to 1 month

• 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

• Level of Inflammatory Markers (A2A)

  Baseline-End of study infusion over 48 hours

• Level of Inflammatory Markers (IL-4)

  Baseline-End of study infusion over 48 hours

Study Arms (2)

Regadenoson Arm

ACTIVE COMPARATOR

1.44 mcg/kg/hour infused over 48 hours

Drug: Regadenoson

Placebo Arm

PLACEBO COMPARATOR

Placebo infused over 48 hours

Drug: Placebo

Interventions

Regadenoson DRUG

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.

Also known as: Lexiscan

Regadenoson Arm

Placebo DRUG

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.

Also known as: Regadenoson Placebo, Lexiscan Placebo, 0.9% Normal Saline

Placebo Arm

Eligibility Criteria

• Age: 10 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Boston Children's Hospital: collaborator
• La Jolla Institute for Allergy & Immunology: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Washington University School of Medicine: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• University of Illinois at Chicago: collaborator
• Medical College of Wisconsin: collaborator
• Duke University: collaborator
• Johns Hopkins University: collaborator
• Wayne State University: collaborator
• Baylor College of Medicine: collaborator
• UCSF Benioff Children's Hospital Oakland: collaborator

Study Sites (12)

Children's Hospital and Research Center at Oakland

Oakland, California, 94609, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 29296811 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

regadenoson; Saline Solution

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. David G. Nathan
• Organization: Dana-Farber Cancer Institute

David_Nathan@dfci.harvard.edu

61746322155

Study Officials

• David Nathan, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 7, 2013
• First Posted: February 11, 2013
• Study Start: July 1, 2013
• Primary Completion: November 10, 2016
• Study Completion: December 12, 2016
• Last Updated: February 7, 2018
• Results First Posted: February 7, 2018

Record last verified: 2018-01

Locations

US (12)