Safety and Efficacy of Sodium Nitrite in Sickle Cell Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01033227
Recruitment Status : Terminated (Low enrollment)
First Posted : December 16, 2009
Results First Posted : February 8, 2017
Last Update Posted : October 17, 2017
Hope Pharmaceuticals
Information provided by (Responsible Party):
Thomas Coates, Children's Hospital Los Angeles

December 15, 2009
December 16, 2009
April 13, 2016
February 8, 2017
October 17, 2017
December 2009
June 2012   (Final data collection date for primary outcome measure)
48 Hour Sodium Nitrite Infusion Safety as Determined by Number of Participants With No Adverse Events [ Time Frame: 48 hours from start of infusion ]
The primary end points will be to determine if a) a 48-hour sodium nitrite infusion is tolerated without a decrease in mean arterial blood pressure by 15mmHg for greater than 2 hours or development of methemoglobin greater than 5% and b) a 48-hour sodium nitrite infusion is safe as determined by monitoring for adverse events
Per the protocol, safety assessments will include physical examinations, vital signs, clinical laboratory tests, ECG, methemoglobin concentration, and reported AEs. [ Time Frame: 0, 8, 16, 24, 32, 40, 48, or 56-72 hours after initiation of sodium nitrite infusion and 30 days after discharge ]
Complete list of historical versions of study NCT01033227 on Archive Site
Secondary End Point [ Time Frame: 48 hours ]
a) reduced the duration and intensity of pain; b) reduced total narcotic analgesic consumption; and c) reduced length of hospitalization.
Adolescent Pediatric Pain Tool, total narcotic analgesic consumption, time between randomization & discharge, near infrared spectroscopy, serum LDH, reticulocyte count, plasma hemoglobin [ Time Frame: 0, 8, 16, 24, 32, 40, 48, and 56-72 hours after initiation of infusion, and 30 days after discharge ]
Not Provided
Not Provided
Safety and Efficacy of Sodium Nitrite in Sickle Cell Disease
A Safety and Efficacy Evaluation of Sodium Nitrite Injection for the Treatment of Vaso-Occlusive Crisis Associated With Sickle Cell Disease
This study will determine if administration of sodium nitrite is safe and can improve small vessel blood flow and tissue oxygenation when given as an additional treatment in patients with acute vaso-occlusive crisis (pain crisis) associated with sickle cell disease.

Nitric oxide (NO) is a naturally occuring chemical that relaxes blood vessels and helps improve blood flow.

The pain associated with vaso-occlusive crisis (pain crisis) in sickle cell disease is caused in part by lack of oxygen and increased tissue acid because blood flow is blocked by stiff sickle red cells. Administration of sodium nitrite should generate nitric oxide in this area of hypoxia and acidosis and improve blood flow.

Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Sickle Cell Disease
Drug: sodium nitrite injection, usp
Sodium nitrite injection, USP will be administered in blocks of six subjects (3 sodium nitrite and 3 no drug). A total of five dose levels are planned, pending safety starting. Drug will be given by continuous infusion infusion for 48 hours starting at 6 nmol/min/kg (10% of the maximal tolerated dose).
Other Name: sodium nitrite
  • No Intervention: No drug
    No study drug administered
  • Experimental: Sodium nitrite injection, USP
    Administration if sodium nitrite injection, USP
    Intervention: Drug: sodium nitrite injection, usp

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
June 2012
June 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

Subjects meeting all of the following criteria will be considered for admission to the study:

  1. Male or female subject aged between 8 and 23 years of age; only patients up to the age of 23 will be studied at Childrens Hospital Los Angeles
  2. Electrophoretic diagnosis of sickle cell disease;
  3. Sudden onset of acute pain involving >=1 sites typical of vaso-occlusive crisis (Vaso-occlusive crisis is defined as acute, severe pain in the extremities, chest, abdomen, or back that can not be explained by other complications of sickle cell disease or by a cause other than sickle cell disease.);
  4. Severe pain requiring parenteral analgesics and hospitalization.
  5. Informed consent obtained from a legal representative or from subjects 18 years of age or older before enrollment;
  6. Being willing and able to be followed for at least 30 days for evaluation.

Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study:

  1. Clinically significant bleeding;
  2. Current drug abuse or participation in methadone program;
  3. Episode of pain requiring hospitalization within 2 weeks prior to current admission;
  4. Other complications of sickle cell disease including cerebrovascular accident, pulmonary hypertension, or seizure;
  5. Pregnancy (confirmed by a serum human chorionic gonadotropin pregnancy test) or breast feeding;
  6. Blood pressure less than 25th percentile for the subject's age and sex on admission or at the time of screening;
  7. Methemoglobinemia >3%;
  8. Anemia with hemoglobin level less than 6 g/dL;
  9. Red blood cell G6PD deficiency, by laboratory testing prior to enrollment;
  10. History of allergy to nitrites or allergy to other substances characterized by dyspnea and cyanosis;
  11. Treatment with allopurinol, a medication that could interfere with nitrite metabolism, within the past 30 days before screening;
  12. Treatment with any investigational drug within the past 30 days;
  13. Significant acute or chronic concomitant diseases (including renal, hepatic, cardiovascular, pulmonary, or oncologic disease, sepsis, pulmonary edema, pulmonary embolism) that would be inconsistent with survival for at least 6 months;
  14. Any subject judged by the clinical investigator or study manager to be inappropriate for the study.
Sexes Eligible for Study: All
8 Years to 23 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Plan to Share IPD: No
Thomas Coates, Children's Hospital Los Angeles
Children's Hospital Los Angeles
Hope Pharmaceuticals
Principal Investigator: Thomas Coates, MD Children's Hospital Los Angeles
Children's Hospital Los Angeles
September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP