Steroid Treatment for Sickle Cell Pain Crisis
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Steroid arm 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 |
Drug: Steroid arm
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
Other Names:
|
| Placebo Comparator: Comparison Group 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. |
Other: Placebo
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
|
Outcome Measures
Primary Outcome Measures
- Pain Scores [30 days]
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 [Through hospitalization, up to 15 days]
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 [30 days]
To describe adverse events, including infection, hypertension, and/or GI bleeding
- Number of Participants With Recurrent Episodes of Pain Within 1 Month of Treatment [30 days]
Number of recurrent episodes of pain within 1 month of treatment
- Number of Days Analgesia Used [Through hospitalization, up to 15 days]
# of days during which the child received parenterally-administered opioids through hospitalization, up to 15 days.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Texas Childrens Hospital | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Baylor College of Medicine
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-17689
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Intervention (Steroids) | Placebo |
|---|---|---|
| Arm/Group 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 | a comparison group who received standard of care therapy for acute chest syndrome, with normal saline substituted in lieu of IV solumedrol (methylprednisolone) and placebo pills in lieu of prednisone tablets (same # of tablets of placebo given as would have been administered to the intervention arm). |
| Period Title: Overall Study | ||
| STARTED | 9 | 9 |
| COMPLETED | 6 | 9 |
| NOT COMPLETED | 3 | 0 |
Baseline Characteristics
| Arm/Group Title | Intervention Arm | Placebo Arm | Total |
|---|---|---|---|
| Arm/Group Description | Receipt of IV pulse of steroids (methylprednisolone) followed by a steroid taper on the subsequent days: 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 | Receipt of usual care, with administration of placebo: 1) normal saline in lieu of IV methylprednisolone followed by 2) placebo tablets in lieu of prednisone tablets. | Total of all reporting groups |
| Overall Participants | 9 | 9 | 18 |
| Age (Count of Participants) | |||
| <=18 years |
9
100%
|
9
100%
|
18
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Inter-Quartile Range) ] | |||
| Mean (Inter-Quartile Range) [years] |
6.5
|
10.6
|
9.6
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
4
44.4%
|
5
55.6%
|
9
50%
|
| Male |
5
55.6%
|
4
44.4%
|
9
50%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
11.1%
|
0
0%
|
1
5.6%
|
| Not Hispanic or Latino |
8
88.9%
|
9
100%
|
17
94.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
8
88.9%
|
9
100%
|
17
94.4%
|
| White |
1
11.1%
|
0
0%
|
1
5.6%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
9
100%
|
9
100%
|
18
100%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analyzed by intent to treat (ITT), with the 3 protocol deviations in the intervention arm (all 3 received placebo) counting toward the intervention arm. |
| Arm/Group Title | Intervention (Steroids) | Placebo Group |
|---|---|---|
| Arm/Group Description | Receipt of pulse IV dose of methylprednisolone followed by a tapering dose of systemic oral corticosteroids (prednisone). | Receipt of usual care, with normal saline in lieu of IV methylprednisolone and placebo tablets in lieu of prednisone tablets. |
| Measure Participants | 9 | 9 |
| Median (Inter-Quartile Range) [score on a scale] |
4.3
|
4.5
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat |
| Arm/Group Title | Steroid Arm | Comparison Group |
|---|---|---|
| Arm/Group Description | Steroid arm: 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 | 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. |
| Measure Participants | 9 | 9 |
| Median (Inter-Quartile Range) [days] |
6.5
|
10.6
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat |
| Arm/Group Title | Steroid Arm | Comparison Group |
|---|---|---|
| Arm/Group Description | Steroid arm: 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 | 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. |
| Measure Participants | 9 | 9 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat |
| Arm/Group Title | Steroid Arm | Comparison Group |
|---|---|---|
| Arm/Group Description | Steroid arm: 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 | 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. |
| Measure Participants | 9 | 9 |
| Count of Participants [Participants] |
0
0%
|
1
11.1%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat |
| Arm/Group Title | Steroid Arm | Comparison Group |
|---|---|---|
| Arm/Group Description | Steroid arm: 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 | 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. |
| Measure Participants | 9 | 9 |
| Median (Full Range) [days] |
4
|
3
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Intervention Arm (Steroids) | Control Group | ||
| Arm/Group Description | Receipt of IV followed by oral systemic corticosteroids | Standard care for acute chest syndrome, with normal saline used in lieu of IV methylprednisolone and placebo tablets used in lieu of oral steroid tablets. | ||
All Cause Mortality |
||||
| Intervention Arm (Steroids) | Control Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Serious Adverse Events |
||||
| Intervention Arm (Steroids) | Control Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Intervention Arm (Steroids) | Control Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Andrea T. Cruz, MD, MPh |
|---|---|
| Organization | Baylor College of Medicine |
| Phone | 832-824-5582 |
| acruz@bcm.edu |
- H-17689