Ignite Creation Date:
2024-05-05 @ 12:11 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00263562
Status:
TERMINATED
Last Update Posted:
2020-07-07
First Post:
2005-12-08
Brief Title:
Steroid Treatment for Sickle Cell Pain Crisis
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Randomized Trial of High-dose Intravenous Methylprednisolone and Steroid Taper for Vaso-occlusive Crises in Sickle Cell Disease
Status:
TERMINATED
Status Verified Date:
2020-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
poor enrollment availability of more effective medications
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 0no pain to 10a lot of pain worst pain 0no pain to 10a lot of pain least pain 0no pain to 10a lot of pain and the amount of pain relief 0no relief to 10complete 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
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 0no pain to 10a lot of pain worst pain 0no pain to 10a lot of pain least pain 0no pain to 10a lot of pain and the amount of pain relief 0no relief to 10complete 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 Lancet1972 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 mgkg 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
1 duration of inpatient admissions
2 to examine the number and type of complications and side effects infection hypertension and GI bleeding
3 to determine rate of recurrent episodes of pain within one month of treatment
4 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
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 Lancet1972 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 mgkg 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
1 duration of inpatient admissions
2 to examine the number and type of complications and side effects infection hypertension and GI bleeding
3 to determine rate of recurrent episodes of pain within one month of treatment
4 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None