Back to resultsArginine Therapy for Sickle Cell Disease Pain
Primary Purpose
Sickle Cell Disease, Vaso-occlusive Pain Episode
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
L-arginine
L-arginine Loading Dose
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring Arginine Therapy
Eligibility Criteria
Inclusion Criteria:
- Established diagnosis of sickle cell disease (SCD); all genotypes
- Pain requiring medical care in an acute care setting (such as the emergency department or ED, hospital ward, day hospital, clinic) not attributable to non-sickle cell causes, that is moderate-to-severe requiring parenteral opioids
Exclusion Criteria:
- Decision to discharge home from the acute care setting
- Hemoglobin less than 5 gm/dL or immediate need for red cell transfusion anticipated within next 12 hours
- Hepatic dysfunction of SGPT greater than 3 times the upper value
- Renal dysfunction of creatinine greater than 1.0
- Mental status or neurological changes
- Acute stroke or clinical concern for stroke
- Pregnancy
- Allergy to arginine
- Two (2) or more ED visits for VOE within the last 7 days prior to CURRENT ED visit
- Hospitalization within 14 days
- Previous randomization in this arginine RCT (patient consented and screen failed before receiving study drug or placebo remains eligible for future participation).
- Use of inhaled nitric oxide, sildenafil or arginine within the last month
- PICU admission from the emergency department
- Hypotension requiring treatment with clinical intervention
- Acidosis with Co2≤ 16
- Newly started on HU for <3 months
- Not an appropriate candidate in the investigator's judgment
- Patient refusal
Sites / Locations
- Children's Healthcare of Atlanta at Hugh Spalding
- Children's Healthcare of Atlanta at Egleston
- Children's Healthcare of Atlanta at Scottish Rite
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
L-Arginine
Loading Dose and L-Arginine
Placebo
Arm Description
Participants will be randomized to receive an intravenous (IV) infusion of L-arginine (100 mg/kg) three times a day until time of discharge from the emergency department (ED) or hospital.
Participants will be randomized to receive an intravenous (IV) infusion of one-time loading dose of L-arginine (200 mg/kg) followed by standard dose (100 mg/kg) three times a day until time of discharge from the emergency department (ED) or hospital.
Participants will be randomized to receive an intravenous (IV) infusion of placebo (normal saline 1-2 ml/kg) three times a day until time of discharge from the emergency department (ED) or hospital.
Outcomes
Primary Outcome Measures
Total Parenteral Opioid Use in IV Morphine Equivalents
The total amount of parenteral opioids used by participants measured in mg/kg of IV morphine equivalents. The total is calculated after study drug delivery for participants in the emergency department (ED) and during hospital stay.
Secondary Outcome Measures
Length of Hospital Stay
The total number of hours spent in the hospital from study drug delivery to time of discharge.
Time to Vaso-occlusive Pain Event (VOE) Resolution in Emergency Department
The total number of hours between study drug delivery and the last parenteral opioid.
Time to Vaso-occlusive Pain Event (VOE) Resolution in Hospital
The total number of hours between study drug delivery and time of last parenteral opioid use, pain relief improved to tolerate oral pain medications
Change in Vaso-occlusive Pain (VOE) Scores
Pain associated with VOE will be measured on a scale of 0-10, by asking subjects to rate their pain level on a subjective scale from 0 to 10, with the ends representing the extreme limits of "no-pain" (0) and "worst pain" (10).
Length of Emergency Department (ED) Stay
Total hours from time of ED triage to ED discharge or hospital admission.
Rate of Emergency Department (ED) Discharge
Number of participants discharged from ED without a hospital ward admission.
Total Opioid Dose (ORAL + Parenteral) in mg/kg IV Morphine Equivalents
Total opioid dose (ORAL + Parenteral) in mg/kg IV morphine equivalents after study drug delivery up to hospital discharge (up to 8 days)
Total Number of Study Drug Doses
The total number of study drug doses given throughout the study period.
Rate of Acute Chest Syndrome
Number of participants who develop acute chest syndrome (not diagnosed prior to study drug delivery) throughout the study period.
Rate of Blood Transfusion
Number of participants requiring a blood transfusion throughout the study period.
Oxygen Saturation Level
Average oxygen saturation level of participants at time of ED arrival
Oxygen Saturation Level
The difference in oxygen saturation levels from emergency department arrival to hospital discharge.
Rate of Return Visits to Emergency Department (ED) Within 72 Hours
Number of ED visits from patients who have been discharged within the previous 72 hours.
Rate of Hospital Re-admissions Within 72 Hours
Number of patients readmitted to the hospital within 72 hours of discharge.
Rate of Return Visits to Emergency Department (ED) Within 30 Days
Number of ED visits from patients who have been discharged within the previous 30 days.
Rate of Hospital Re-admissions With 30 Days
Number of patients readmitted to the hospital within 30 days of discharge.
Full Information
NCT ID
NCT02536170
First Posted
August 27, 2015
Last Updated
August 23, 2023
Sponsor
Emory University
Collaborators
Children's Healthcare of Atlanta, National Center for Complementary and Integrative Health (NCCIH)
1. Study Identification
Unique Protocol Identification Number
NCT02536170
Brief Title
Arginine Therapy for Sickle Cell Disease Pain
Official Title
Phase 2 Randomized Control Trial of Arginine Therapy for Pediatric Sickle Cell Disease Pain
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
February 21, 2021 (Actual)
Study Completion Date
February 21, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
Children's Healthcare of Atlanta, National Center for Complementary and Integrative Health (NCCIH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of this study is to determine whether giving extra arginine, a simple amino acid, to patients with sickle cell disease seeking treatment for a pain crisis (vaso-occlusive painful events (VOE) will decrease pain scores, decrease the need for pain medications or decrease length of hospital stay or emergency department visit. Funding Source - FDA OOPD.
Detailed Description
The purpose of this study is to determine the effects of IV L-arginine hydrochloride therapy in children with sickle cell disease (SCD) and vaso-occlusive pain events (VOE). Specifically, the impact on total opioid use (mg/kg) over the duration of their emergency department (ED) visit and hospital stay will be evaluated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Vaso-occlusive Pain Episode
Keywords
Arginine Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
108 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L-Arginine
Arm Type
Experimental
Arm Description
Participants will be randomized to receive an intravenous (IV) infusion of L-arginine (100 mg/kg) three times a day until time of discharge from the emergency department (ED) or hospital.
Arm Title
Loading Dose and L-Arginine
Arm Type
Experimental
Arm Description
Participants will be randomized to receive an intravenous (IV) infusion of one-time loading dose of L-arginine (200 mg/kg) followed by standard dose (100 mg/kg) three times a day until time of discharge from the emergency department (ED) or hospital.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be randomized to receive an intravenous (IV) infusion of placebo (normal saline 1-2 ml/kg) three times a day until time of discharge from the emergency department (ED) or hospital.
Intervention Type
Drug
Intervention Name(s)
L-arginine
Other Intervention Name(s)
Arginine
Intervention Description
L-arginine will be dispensed intravenously (IV) in the standard dose of 100 mg/kg three times a day until discharge from the emergency department (ED) or hospital.
Intervention Type
Drug
Intervention Name(s)
L-arginine Loading Dose
Other Intervention Name(s)
Arginine
Intervention Description
One loading dose of L-arginine will be dispensed intravenously (IV) at 200 mg/kg
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo of intravenous (IV) normal saline 1-2 ml/kg three times a day until discharge from the emergency department (ED) or hospital.
Primary Outcome Measure Information:
Title
Total Parenteral Opioid Use in IV Morphine Equivalents
Description
The total amount of parenteral opioids used by participants measured in mg/kg of IV morphine equivalents. The total is calculated after study drug delivery for participants in the emergency department (ED) and during hospital stay.
Time Frame
Post study drug delivery to discharge from the hospital (Up to 8 days)
Secondary Outcome Measure Information:
Title
Length of Hospital Stay
Description
The total number of hours spent in the hospital from study drug delivery to time of discharge.
Time Frame
Discharge (Up to 8 days)
Title
Time to Vaso-occlusive Pain Event (VOE) Resolution in Emergency Department
Description
The total number of hours between study drug delivery and the last parenteral opioid.
Time Frame
Post study drug delivery (Up to 8 hours)
Title
Time to Vaso-occlusive Pain Event (VOE) Resolution in Hospital
Description
The total number of hours between study drug delivery and time of last parenteral opioid use, pain relief improved to tolerate oral pain medications
Time Frame
Post study drug delivery until discharge (up to 8 days)
Title
Change in Vaso-occlusive Pain (VOE) Scores
Description
Pain associated with VOE will be measured on a scale of 0-10, by asking subjects to rate their pain level on a subjective scale from 0 to 10, with the ends representing the extreme limits of "no-pain" (0) and "worst pain" (10).
Time Frame
Baseline, Time of discharge (Up to 8 days)
Title
Length of Emergency Department (ED) Stay
Description
Total hours from time of ED triage to ED discharge or hospital admission.
Time Frame
Until discharge or Hospital Admission (Up to 24 hours)
Title
Rate of Emergency Department (ED) Discharge
Description
Number of participants discharged from ED without a hospital ward admission.
Time Frame
Post emergency department admission (Up to 24 hours)
Title
Total Opioid Dose (ORAL + Parenteral) in mg/kg IV Morphine Equivalents
Description
Total opioid dose (ORAL + Parenteral) in mg/kg IV morphine equivalents after study drug delivery up to hospital discharge (up to 8 days)
Time Frame
Post study drug delivery up to hospital discharge (Up to 8 days)
Title
Total Number of Study Drug Doses
Description
The total number of study drug doses given throughout the study period.
Time Frame
Duration of study (Up to 8 days)
Title
Rate of Acute Chest Syndrome
Description
Number of participants who develop acute chest syndrome (not diagnosed prior to study drug delivery) throughout the study period.
Time Frame
Duration of study (Up to 8 days)
Title
Rate of Blood Transfusion
Description
Number of participants requiring a blood transfusion throughout the study period.
Time Frame
Duration of study (Up to 8 days)
Title
Oxygen Saturation Level
Description
Average oxygen saturation level of participants at time of ED arrival
Time Frame
At time of Emergency Department Admission
Title
Oxygen Saturation Level
Description
The difference in oxygen saturation levels from emergency department arrival to hospital discharge.
Time Frame
At time of hospital admission and at time of Hospital discharge (Up to 8 days)
Title
Rate of Return Visits to Emergency Department (ED) Within 72 Hours
Description
Number of ED visits from patients who have been discharged within the previous 72 hours.
Time Frame
Post hospital discharge (within 72 hours)
Title
Rate of Hospital Re-admissions Within 72 Hours
Description
Number of patients readmitted to the hospital within 72 hours of discharge.
Time Frame
Post hospital discharge (within 72 hours)
Title
Rate of Return Visits to Emergency Department (ED) Within 30 Days
Description
Number of ED visits from patients who have been discharged within the previous 30 days.
Time Frame
Post hospital discharge (within 30 days)
Title
Rate of Hospital Re-admissions With 30 Days
Description
Number of patients readmitted to the hospital within 30 days of discharge.
Time Frame
Post hospital discharge (within 30 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Established diagnosis of sickle cell disease (SCD); all genotypes
Pain requiring medical care in an acute care setting (such as the emergency department or ED, hospital ward, day hospital, clinic) not attributable to non-sickle cell causes, that is moderate-to-severe requiring parenteral opioids
Exclusion Criteria:
Decision to discharge home from the acute care setting
Hemoglobin less than 5 gm/dL or immediate need for red cell transfusion anticipated within next 12 hours
Hepatic dysfunction of SGPT greater than 3 times the upper value
Renal dysfunction of creatinine greater than 1.0
Mental status or neurological changes
Acute stroke or clinical concern for stroke
Pregnancy
Allergy to arginine
Two (2) or more ED visits for VOE within the last 7 days prior to CURRENT ED visit
Hospitalization within 14 days
Previous randomization in this arginine RCT (patient consented and screen failed before receiving study drug or placebo remains eligible for future participation).
Use of inhaled nitric oxide, sildenafil or arginine within the last month
PICU admission from the emergency department
Hypotension requiring treatment with clinical intervention
Acidosis with Co2≤ 16
Newly started on HU for <3 months
Not an appropriate candidate in the investigator's judgment
Patient refusal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Morris, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Healthcare of Atlanta at Hugh Spalding
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Children's Healthcare of Atlanta at Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Children's Healthcare of Atlanta at Scottish Rite
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
36322873
Citation
Bakshi N, Liu Z, Gillespie S, Keesari R, Leake D, Khemani K, Kumari P, Rees CA, Dampier C, Morris CR. Patient-reported outcomes in children with sickle cell disease at presentation for an acute pain episode. Blood Adv. 2023 Sep 12;7(17):5103-5107. doi: 10.1182/bloodadvances.2021006794. No abstract available.
Results Reference
background
PubMed Identifier
34724240
Citation
Reyes LZ, Figueroa J, Leake D, Khemani K, Kumari P, Bakshi N, Lane PA, Dampier C, Morris CR. Safety of intravenous arginine therapy in children with sickle cell disease hospitalized for vaso-occlusive pain: A randomized placebo-controlled trial in progress. Am J Hematol. 2022 Jan 1;97(1):E21-E24. doi: 10.1002/ajh.26396. Epub 2021 Nov 12. No abstract available.
Results Reference
result
PubMed Identifier
32384147
Citation
Morris CR, Brown LAS, Reynolds M, Dampier CD, Lane PA, Watt A, Kumari P, Harris F, Manoranjithan S, Mendis RD, Figueroa J, Shiva S. Impact of arginine therapy on mitochondrial function in children with sickle cell disease during vaso-occlusive pain. Blood. 2020 Sep 17;136(12):1402-1406. doi: 10.1182/blood.2019003672.
Results Reference
derived
Learn more about this trial
Arginine Therapy for Sickle Cell Disease Pain
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