Hydroxyurea in the Emergency Room to Lessen Pain in Sickle Cell Crisis (HELPS)

Protocol for the Administration of Hydroxyurea During Painful Vaso-occlusive Crisis in Sickle Cell Anemia

This study will investigate the safety, tolerability and potential for the use of up to three daily doses of 30-40 mg/kg HU (daily) upon hospitalization for painful vaso-occlusive crises .

Study Overview

• Status: Unknown
• Conditions: Anemia, Sickle Cell; Anemia; Sickle-Cell, With Crisis
• Intervention / Treatment: Drug: Hydroxyurea

Detailed Description

Sickle cell anemia (SCA) is a hereditary hemoglobinopathy; complications of the disease include, spleen enlargement, acute chest syndrome, pulmonary hypertension, stroke and cumulative damage to multiple organs, and painful vaso-occlusive crises (VOC). In Brazil, about 3,500 children are born each year with DF, and the number of individuals with sickle cell disease (DF) in the country is estimated between 25,000 and 30,000 (ANVISA 2012; BRAZIL, 2012).

Hydroxyurea (HU, or hydroxycarbamide) is the only drug approved to date by the American FDA for use in adults with sickle cell disease. The drug modifies the disease process, improving hematological parameters and the hospitalization time of patients, as well as the frequency of vaso-occlusive crises.In addition to its proven effects during chronic use, experimental data indicate that HU has immediate anti-inflammatory effects.

In addition to its proven effects during chronic use, experimental data indicate that HU has immediate anti-inflammatory effects. This study will investigate the safety, tolerability and potential for the use of up to three daily doses of 30-40 mg/kg HU (daily) upon hospitalization for VOC.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Recruiting
    • Hemorio
    • Contact: Thais Oliveira, B.Sc.; Phone Number: 2212 +55 (21) 2505-0750; Email: cdi@hemorio.rj.gov.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of homozygous sickle cell anemia (HbSS).
• Hospitalization due to onset of uncomplicated vaso-occlusive crisis (with pain scale≥6 within the last 24 h), confirmed by clinical evaluation.
• Documented and written informed consent

Exclusion Criteria:

• Confirmed or suspected pregnancy.
• Initiation of painful crisis> 72h.
• Blood transfusion during the last 8 weeks.
• Admission to Emergency Room due to pain in the last 4 weeks.
• Neutrophil count <2.5 x 109/L or platelet count <95.0 x 109 / L or Hb <4.5 g / dL
• Weight <38 Kg or> 95 Kg.
• Interval longer than 8h since arrival at center.
• Non-consent to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control (No Hydroxyurea); Patients in VOC will be treated according to the center's usual practice and analgesia protocol.
Experimental: Hydroxyurea; Patients in VOC will receive up to three daily doses of 30-40 mg / kg hydroxyurea.	Drug: Hydroxyurea; Patients hospitalized for uncomplicated pain crisis with a pain scale of ≥ 6 during the last 24 hours will receive a dose of 30-40 mg / kg hydroxyurea. This same dose of hydroxyurea will be repeated at 24 h and 48 h after the first dose of hydroxyurea, with dose suspension if the patient is discharged within 48 hours. Patients will also receive the center's usual practice and analgesia protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events	as assessed by CTCAE version 4.03	up to 15 days post last dose
Number of participants with altered laboratory values related to treatment		up to 15 days post last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time until hospital discharge		Average, up to 7 days post admission
Total opioid use (mg of IV morphine)		From study inclusion until hospital discharge (average, up to 7 days post admission)
Pain score	Numeric pain score rating (0 to 10; 0 = no pain, 10 = worst pain)	From admission until hospital discharge (average, up to 7 days post admission)

Collaborators and Investigators

• Sponsor: Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Anticipated): April 1, 2017
• Study Completion (Anticipated): July 1, 2017

Study Registration Dates

• First Submitted: January 30, 2017
• First Submitted That Met QC Criteria: February 20, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: February 20, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia; Anemia, Sickle Cell; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: Hemorio 397/16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO