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Steroid Treatment for Sickle Cell Pain Crisis

Primary Purpose

Sickle Cell Disease, Vaso-occlusive Crisis

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Steroid arm
Placebo
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Sickle cell disease, vaso-occlusive crisis, steroid treatment

Eligibility Criteria

8 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Sickle cell and acute pain Age 8 and up English or Spanish-speaking Exclusion Criteria: Fever greater than 101 Acute chest syndrome or pneumonia Other SS complications (sequestration, aplastic crisis) Other explanation for pain (chronic, AVN, surgical) History of GI bleeding, HTN, or hyperglycemia/DM

Sites / Locations

  • Texas Childrens Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Steroid arm

Comparison Group

Arm Description

Receipt of methyprednisolone pulse dose: 15mg/kg to a maximum of 1 gram; following this, the patients also received a steroid taper with oral prednisone:Day 2: Prednisone 2mg/kg PO BID Day 3: Prednisone 2mg/kg PO daily Day 4: Prednisone 1mg/kg PO daily Day 5: Prednisone 1mg/kg PO daily

Patients receiving usual care, with receipt of placebo (saline in lieu of intravenous methylprednisolone infusion or a number of placebo pills equivalent in number to what would have been received for the prednisone.

Outcomes

Primary Outcome Measures

Pain Scores
Severity of pain using a 10-point scale ranging from 1-10, with higher numbers corresponding to worsening pain.

Secondary Outcome Measures

Duration of Hospitalization
Length of stay (from emergency department arrival to discharge from the inpatient unit), in days, through hospitalization, up to 15 days
Number of Participants With Complications and Adverse Events
To describe adverse events, including infection, hypertension, and/or GI bleeding
Number of Participants With Recurrent Episodes of Pain Within 1 Month of Treatment
Number of recurrent episodes of pain within 1 month of treatment
Number of Days Analgesia Used
# of days during which the child received parenterally-administered opioids through hospitalization, up to 15 days.

Full Information

First Posted
December 8, 2005
Last Updated
June 22, 2020
Sponsor
Baylor College of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00263562
Brief Title
Steroid Treatment for Sickle Cell Pain Crisis
Official Title
Randomized Trial of High-dose Intravenous Methylprednisolone and Steroid Taper for Vaso-occlusive Crises in Sickle Cell Disease
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
poor enrollment, availability of more effective medications
Study Start Date
December 1, 2005 (Actual)
Primary Completion Date
June 13, 2008 (Actual)
Study Completion Date
June 13, 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine

4. Oversight

5. Study Description

Brief Summary
The painful episode is the most common problem experienced by children with sickle cell disease. Although various treatments are available during painful episodes, the medication most commonly given for pain is a pain medication such as morphine. Fluids are also used. Even with these treatments, many children still have severe pain that is difficult to control. In addition to pain medications, there are other medications that may be useful. Methylprednisolone (solumedrol) and prednisone are a group of medications called steroids that may be helpful for painful episodes. These medications are known to lower the amount of inflammation (this means swelling, tenderness, and soreness) in the body. Because this medication may help with your pain, you are being asked to be a part of this study. These types of medications are used in other illnesses such as asthma, especially during times when the illness has gotten worse. The main purpose of this study is to see if the methylprednisolone and prednisone will lower the amount of pain and the length of hospital stay. In addition to the pain medication you will normally receive, you will be assigned to one of 2 groups: 1) the experimental group with the active form of the medicine, or 2) a comparison group without the active form of the medicine. In either group, you will still receive all of the treatments you would normally receive for a painful episode, including pain medicines and fluids. You and your doctors will not know what group you will be assigned. If you decide to be a part of the study the following will happen: For the first 5 days, you will be asked to: 1) describe your current pain (0=no pain to 10=a lot of pain), worst pain (0=no pain to 10=a lot of pain), least pain (0=no pain to 10=a lot of pain), and the amount of pain relief (0=no relief to 10=complete relief); 2) describe any signs or symptoms you feel, including filling out a pain scale form each day; 3) and take the medicines for 5 days, either at home or when in the hospital. Thirty days after the study, a study researcher will call and will ask questions about your pain, any painful episodes, and any medications you had. If you are discharged home sooner than 5 days after the start of the study, research staff will call you to ask you these questions, remind you to fill out your pain forms, and remind you to take your medicine. If you are discharged home, you will be given pain scales to fill out each day at home.
Detailed Description
In the United States, 9% of African Americans have sickle cell trait and 1 in 600 has sickle cell disease. Vaso- occlusive crises in sickle cell disease remain a frequent cause of severe pain, leading to emergency room visits, hospitalizations, and dependence upon narcotics for analgesia. Current treatments for vaso-occlusive crises includes IV analgesia with narcotics, NSAIDS, and hydration. Admissions can be frequent, prolonged, and can significantly diminish quality of life. Understanding the pathophysiology of vaso-occlusive crises helps to find possible treatments. The etiology of vaso- occlusive crises includes HbS polymerization; sickle erythrocyte polymerization; endothelial damage; and inflammation, reperfusion injury, and oxidant radical production (Steinberg et al, Hematology, 2004). For example, hydroxyurea works by increasing the amount of fetal hemoglobin (HbF) and thus inhibiting polymerization, and reduces the incidence of pain by nearly 50%. Glucocorticoids would be expected to exert effects on the endothelium and inflammation. Vaso-occlusive crises share similar features with other inflammatory processes, including clinical symptoms of swelling, erythema, and warmth; and laboratory findings of leukocytosis and elevated ESR. It has previously been theorized that glucocorticoids, which are used in many other inflammatory disorders, could decrease the duration or severity of vaso-occlusive crises. Methylprednisolone is a corticosteroid which decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability (Takemoto, et al 2004). A randomized, placebo-controlled study of 2 doses of intravenous methylprednisolone for vaso-occlusive crisis showed that the duration of severe pain and the need for inpatient analgesia was decreased in patients who received methylprednisolone; however the intervention patients had more rebound attacks than those who received placebo. (Griffin et al, NEJM, 1994) Previous studies have examined long-term administration of steroid hormones including testosterone, progesterone, and medroxyprogesterone to patients with sickle cell disease. In placebo-controlled crossover trials, patients who received steroids had fewer vaso-occlusive episodes than placebo-treated patients (Isaacs et al, Lancet,1972; DeCeulaer et al, Lancet, 1982). Initial reports of glucocorticoids for vaso-occlusive crisis include an uncontrolled report of hydrocortisone as adjunctive therapy for VOC (Araujo et al, Blood, 1990). A case report showed efficacy of dexamethasone for vaso-occlusive crisis in children (Robinson et al, Lancet, 1979). The mechanism of steroids effect is uncertain. In acute chest syndrome, which shares many clinical features with vaso-occlusive crises, intravenous therapy with dexamethasone has been shown to reduce the length of hospital stay, prevent clinical deterioration, and reduce the need for blood transfusion (Bernini et al, Blood, 1998). In a placebo-controlled trial of high-does methylprednisolone for VOC, patients with severe pain requiring hospital admission were randomized to receive methylprednisolone or placebo (15 mg/kg to maximum 1 gram) at admission and again 24 hours later. The duration of inpatient analgesia was significantly shorter in patients who received methylprednisolone. However, patients who received methylprednisolone were much more likely to be readmitted shortly after finishing therapy. In addition, the study was criticized because patients did not rate their pain, and very few patients received patient-controlled analgesia while hospitalized. Since this trial was published, there have been other advances in the standard management of VOC. Ketorolac, a non-steroidal analgesic, is now a standard adjunctive therapy, and most patients are quickly placed on patient-controlled analgesia. In addition, more patients now receive chronic, preventative therapies such as hydroxyurea and chronic transfusions. We are therefore interested in repeating and expanding upon the results obtained several years ago and in evaluating the role of steroids if given over a slightly longer period of time. The primary objective of this study is to determine whether the use of high-dose methylprednisolone followed by steroid taper decreases the duration of hospitalization and severity of pain in VOC of sickle cell disease. Primary Hypothesis: The experimental group treated with high-dose methylprednisolone and steroid taper plus conventional therapy will have an improvement in pain scores using a 10-point scale. In addition, the secondary objectives were: duration of inpatient admissions to examine the number and type of complications and side effects (infection, hypertension, and GI bleeding) to determine rate of recurrent episodes of pain within one month of treatment. to determine whether the amount of analgesic used will decrease during the hospitalization, as measured by the # of days in which IV opioids were given.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Vaso-occlusive Crisis
Keywords
Sickle cell disease, vaso-occlusive crisis, steroid treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Steroid arm
Arm Type
Experimental
Arm Description
Receipt of methyprednisolone pulse dose: 15mg/kg to a maximum of 1 gram; following this, the patients also received a steroid taper with oral prednisone:Day 2: Prednisone 2mg/kg PO BID Day 3: Prednisone 2mg/kg PO daily Day 4: Prednisone 1mg/kg PO daily Day 5: Prednisone 1mg/kg PO daily
Arm Title
Comparison Group
Arm Type
Placebo Comparator
Arm Description
Patients receiving usual care, with receipt of placebo (saline in lieu of intravenous methylprednisolone infusion or a number of placebo pills equivalent in number to what would have been received for the prednisone.
Intervention Type
Drug
Intervention Name(s)
Steroid arm
Other Intervention Name(s)
Systemic corticosteroid receipt
Intervention Description
Day 1: Solumedrol 15 mg/kg (maximum 1 gram) Day 2: Prednisone 2mg/kg PO BID Day 3: Prednisone 2mg/kg PO daily Day 4: Prednisone 1mg/kg PO daily Day 5: Prednisone 1mg/kg PO daily
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Patients received normal saline in lieu of intravenously-administered methylprednisolone and placebo pills equal in number to the steroid pills received in the steroid arm
Primary Outcome Measure Information:
Title
Pain Scores
Description
Severity of pain using a 10-point scale ranging from 1-10, with higher numbers corresponding to worsening pain.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Duration of Hospitalization
Description
Length of stay (from emergency department arrival to discharge from the inpatient unit), in days, through hospitalization, up to 15 days
Time Frame
Through hospitalization, up to 15 days
Title
Number of Participants With Complications and Adverse Events
Description
To describe adverse events, including infection, hypertension, and/or GI bleeding
Time Frame
30 days
Title
Number of Participants With Recurrent Episodes of Pain Within 1 Month of Treatment
Description
Number of recurrent episodes of pain within 1 month of treatment
Time Frame
30 days
Title
Number of Days Analgesia Used
Description
# of days during which the child received parenterally-administered opioids through hospitalization, up to 15 days.
Time Frame
Through hospitalization, up to 15 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Sickle cell and acute pain Age 8 and up English or Spanish-speaking Exclusion Criteria: Fever greater than 101 Acute chest syndrome or pneumonia Other SS complications (sequestration, aplastic crisis) Other explanation for pain (chronic, AVN, surgical) History of GI bleeding, HTN, or hyperglycemia/DM
Facility Information:
Facility Name
Texas Childrens Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Steroid Treatment for Sickle Cell Pain Crisis

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