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| ID | Type | Description | Link |
|---|---|---|---|
| PECARN Protocol Number 050 | Other Identifier | Pediatric Emergency Care Applied Research Network | |
| UG3HL148560 | U.S. NIH Grant/Contract | View source | |
| 2021P003315 | Other Identifier | Emory IRB |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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The trial is designed to test intravenous (IV) arginine therapy in children with sickle cell disease (SCD) and vaso-occlusive painful episodes (VOE) to further knowledge on efficacy and safety of this orphan drug.
Pain is a clinical hallmark of sickle cell disease (SCD), and a significant problem in emergency medicine. Vaso-occlusive painful episodes (VOE) are common, debilitating, and a medical emergency. VOE are the leading cause of hospitalizations, emergency department (ED) visits, missed school, and are associated with an increased mortality rate. Symptomatic relief with analgesics and hydration are the only currently available treatments, and these have not changed in decades. Episodic periods of severe pain lead to high use of health care resources, with high readmission rates. A 2010 health care utilization report revealed that 20% of patients with SCD experienced ≥3 ED encounters per year. Hospital admission rates for VOE are approximately 60% for children with SCD and VOE. Many children with SCD also live with daily pain to some extent that their families try to control at home through various methods. It is when the pain becomes acutely worse, and unbearable, that they present to the ED in acute distress.
A significant evidence gap exists for best treatment of VOE and novel approaches to SCD/VOE that can be utilized in the ED and hospital ward are critically needed. Interventions that target underlying mechanisms of SCD pain in addition to providing symptomatic relief are worth pursuing.
Vaso-occlusion is believed to be the root cause of sickle cell pain. Nitric oxide (NO) is a free radical and a potent vasodilator that regulates vascular homeostasis and plays a role in SCD vaso-occlusion. NO has properties that can impact every aspect of SCD, and NO dysregulation is a common denominator among varied mechanisms of sickle vasculopathy. NO is produced in the endothelium from its obligate substrate L-arginine, which is converted to citrulline by a family of enzymes, the NO synthases (NOS). Although NOS expression and activity is increased, SCD is characterized by a state of NO resistance, NO inactivation, and impaired NO bioavailability. Under conditions of increased hemolysis, inflammation or oxidative stress, the compensatory upregulation of NO likely becomes overwhelmed and ineffective. Vascular dysfunction is the end result, due to complex and multifactorial interactions.
SCD is an arginine deficiency syndrome. Normal arginine metabolism is impaired for many reasons. Plasma arginine concentration decreases significantly in both adults and children with VOE and is associated with low nitric oxide (NO) and nitrogen dioxide (NO2) levels (NOx). It was observed that lowest arginine levels were found in children requiring admission for VOE, with arginine levels returning to baseline during convalescence in the hospital. Of interest, low plasma arginine concentration alone was a sensitive predictor for admission, while NOx levels were not, suggesting a function for arginine bioavailability in VOE severity that goes beyond NO. Although adults with SCD are arginine deficient at steady-state, children have plasma levels that are similar to normal controls. Alterations in the arginine metabolome differ in children vs. adults. An arginine deficiency develops with age and is influenced by acute events and chronic end organ damage that worsens over time. Children may therefore be more responsive to arginine therapy during an acute pain event compared to adults.
Arginine is a safe nutritional supplement that is FDA approved in parenteral form for growth hormone stimulation testing, with nearly 50 years of safety experience through its common use by endocrinologists. Experience with both oral and parenteral arginine therapy in sickle cell disease is growing. When arginine is given to SCD patients at steady-state, a paradoxical decrease in NOx occurs that is not overcome by higher doses, clearly indicating that arginine is metabolized differently in SCD compared to controls. However when arginine is given during VOE, a robust dose-dependent increase in NOx is observed. This indicates that arginine is also metabolized differently in SCD at steady-state (baseline) compared to times of acute illness including pain. Low dose arginine therapy is likely to be subtherapeutic in SCD; higher levels of plasma arginine are likely needed to overcome multi-factorial effects on global arginine bioavailability, and accelerated arginine consumption during VOE compared to baseline.
The trial is designed as a double-blind, placebo controlled, randomized, phase 3, multi-center trial of IV arginine therapy in children with VOE in SCD to further knowledge on efficacy and safety of the therapy. The exploratory objective is to more fully characterize the arginine metabolome in children with SCD during VOE, and evaluate the effects of arginine therapy on global arginine bioavailability and mitochondrial function together with important clinical outcomes of time to VOE resolution, pain scores, total parenteral opioid use, Patient-Reported Outcomes (PROs), and hospital length of stay in children with SCD and VOE.
Participants are randomized to receive 21 doses of IV arginine or a placebo, administered over 7 to 8 days (depending on what time of day the study drug was first administered on Day 1). Participants will be followed for up to 28 days following hospital discharge.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-Arginine Hydrochloride | Experimental | Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. |
|
| Placebo | Placebo Comparator | Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-Arginine Hydrochloride | Drug | A one-time L-arginine hydrochloride loading dose of 200 mg/kg will be administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID). |
| Measure | Description | Time Frame |
|---|---|---|
| Time-to-crisis Resolution | The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery. | From study drug delivery to last IV opioid treatment (up to 1,724.1 hours) |
| Measure | Description | Time Frame |
|---|---|---|
| Total Parenteral Opioid Use | Total parenteral opioid use is assessed as morphine equivalents in milligrams per kilogram (mg/kg). | From the time of IV placement throughout opioid treatment (up to 1,724.1 hours) |
| Change in Pain Score |
| Measure | Description | Time Frame |
|---|---|---|
| Time-to-crisis Resolution By Sex | The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery. | From study drug delivery to last IV opioid treatment (up to 1,724.1 hours) |
| Time-to-crisis Resolution By Race |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Claudia Morris, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States | ||
| UCSF Benioff Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38527291 | Background | Korman R, Hatabah D, Brown LA, Harris F, Wilkinson H, Rees CA, Bakshi N, Archer DR, Dampier C, Morris CR. Impact of arginine therapy on kyotorphin in children with sickle cell disease and vaso-occlusive pain. Blood Adv. 2024 Jun 25;8(12):3267-3271. doi: 10.1182/bloodadvances.2023012209. | |
| 35426778 | Background | Onalo R, Cilliers A, Cooper P, Morris CR. Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial. Am J Respir Crit Care Med. 2022 Jul 1;206(1):70-80. doi: 10.1164/rccm.202108-1930OC. |
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De-identified individual participant data that underlie the results published for this study will be made available for sharing with other researchers.
Individual participant data will be made available for sharing after publication of findings from this study
Interested investigators can request de-identified data by sending an email to the principal investigator.
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Participants were recruited from ten children's hospitals in the United States. Participant enrollment began June 21, 2021 and all follow-up assessments were completed by July 11, 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | L-Arginine Hydrochloride | Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID). |
| FG001 | Placebo | Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | L-Arginine Hydrochloride | Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time-to-crisis Resolution | The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery. | Posted | Mean | Standard Deviation | hours | From study drug delivery to last IV opioid treatment (up to 1,724.1 hours) |
|
Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | L-Arginine Hydrochloride | Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain | General disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdomial pain | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Claudia Morris, MD | Emory University | 404-785-7141 | claudia.r.morris@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 1, 2020 | Jul 9, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 21, 2022 | Feb 21, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| Normal saline | Other | A placebo of normal saline will be administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID). |
|
Pain is assessed using a scale from 0 to 10, where 10 is the highest pain level. Daily highest and lowest pain scores are recorded. The change in score is calculated by subtracting the score at discharge from the score at the time of presentation.
| Time of presentation and on the day of discharge (up to 554.8 days) |
| Change in Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Score | The PROMIS Pain Interference instrument is an 8-item, self-administered survey that assesses the interference of pain on daily activities. Participants are asked to respond to questions regarding the extent of their pain. Responses range from 1 to 5, where 1 represents "not at all" and 5 represents "very much". Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of pain interference compared to the reference population, while scores higher than 50 indicate greater pain interference compared to the reference population. The change in score is calculated by subtracting the score at the time of discharge from the score from within 12 hours of study drug delivery. The change in score is calculated by subtracting the score at discharge from the score within 12 hours of study drug delivery. | Within 12 hours of study drug delivery, and on the day of discharge (up to 554.8 days) |
| Change in PROMIS Pain Behavior Score | The PROMIS Pain Behavior instrument is an 8-item, self-administered survey that assesses external manifestations of pain. Participants are asked to respond to questions regarding the extent of their pain. Responses range from 1 to 5, where 1 represents "never" and 5 represents "always". Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of pain behavior compared to the reference population, while scores higher than 50 indicate greater pain behavior compared to the reference population. The change in score is calculated by subtracting the score at discharge from the score within 12 hours of study drug delivery. | Within 12 hours of study drug delivery, and on the day of discharge (up to 554.8 days) |
| Change in PROMIS Fatigue Score | The PROMIS Fatigue instrument is an 8-item, self-administered survey that assesses fatigue level within the past seven days. Participants are asked to respond to questions regarding fatigue frequency. Responses range from 1 to 5, where 1 represents "never" and five represents "always". Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of fatigue compared to the reference population, while scores higher than 50 indicate greater fatigue compared to the reference population. The change in score is calculated by subtracting the score at discharge from the score within 12 hours of study drug delivery. | Within 12 hours of study drug delivery and on the day of discharge (up to 554.8 days) |
The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery. |
| From study drug delivery to last IV opioid treatment (up to 1,724.1 hours) |
| Time-to-crisis Resolution By Ethnicity | The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery. | From study drug delivery to last IV opioid treatment (up to 1,724.1 hours) |
| Medication Quantification Score (MQS) | Medication Quantification Score (MQS) is a tool to objectively quantify pain. The MQS is a validated score calculated based off of daily doses of pain related medications (including acetaminophen, aspirin, NSAIDs, and antidepressants). The MQS is a single numeric value for a patient's pain medication profile. This number is used to track pain levels through a treatment course. | Pre-dose and on day of discharge (up to 2 months) |
| Hospital Length of Stay | Hospital length of stay in days is recorded. | Up to 6 months |
| Pediatric PROMIS Score | The Pediatric PROMIS assesses five domains of health with in a 35-item instrument. The survey is completed by patients ages 8-17 years of age and parents of children ages 5-17 years of age. The domains included are: pain behavior (8 items), pain interference (8 items), pain intensity (1 item), physical stress experiences (8 items), and fatigue (10 items). Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of the concept being measured compared to the reference population, while scores higher than 50 indicate a greater amount of the concept being measured (e.g., more fatigue) compared to the reference population. | Within 12 hours of study drug delivery and on the day of discharge (up to 2 months) |
| PedsQL SCD Pain and Hurt Scale Score | The Pain and Hurt scale of the PedsQL SCD module has 9 items asking how much of a problem each item has been during the past month. Responses to items are given on a 5-point Likert scale where 0 = never a problem and 4 = almost always a problem. Items are reversed and transformed to a scale of 0 to 100 then the mean score for the scale is calculated. The total score for the Pain and Hurt scale ranges from 0 to 100 with higher scores indicating greater quality of life and lower SCD symptoms. | Within 12 hours of study drug delivery and on the day of discharge (up to 2 months) |
| PedsQL SCD Pain Impact Scale Score | The Pain Impact scale of the PedsQL SCD module has 10 items asking how much of a problem each item has been during the past month. Responses to items are given on a 5-point Likert scale where 0 = never a problem and 4 = almost always a problem. Items are reversed and transformed to a scale of 0 to 100 then the mean score for the scale is calculated. The total score for the Pain Impact scale ranges from 0 to 100 with higher scores indicating greater quality of life and lower SCD symptoms. | Within 12 hours of study drug delivery and on the day of discharge (up to 2 months) |
| Arginine Bioavailability | Peak plasma arginine concentration is assessed via pharmacokinetic study. | Pre-Dose, Day 2, after 21 doses (Day 7 or 8) or at discharge (if discharged prior to Dose 21) |
| Mitochondrial Function | Mitochondrial respiratory complex activities are measured to estimate mitochondrial function. | Pre-Dose, Day 2, after 21 doses (Day 7 or 8) or at discharge (if discharged prior to Dose 21) |
| San Francisco |
| California |
| 94158 |
| United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010 | United States |
| Children's Healthcare of Atlanta at Hughes Spalding | Atlanta | Georgia | 03322 | United States |
| Children's Healthcare of Atlanta at Egleston | Atlanta | Georgia | 30322 | United States |
| Washington University/St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Texas Children's Hospital/Baylor College of Medicine | Houston | Texas | 77030 | United States |
| Medical College of Wisconsin/Wisconsin Children's Hospital | Wauwatosa | Wisconsin | 53226 | United States |
| 34724240 | Background | 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. |
| 32384147 | Background | 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. |
| 33075179 | Background | Onalo R, Cooper P, Cilliers A, Vorster BC, Uche NA, Oluseyi OO, Onalo VD, Zubairu Y, Ayodele-Kehinde AU, Damilare OM, Figueroa J, Morris CR. Randomized control trial of oral arginine therapy for children with sickle cell anemia hospitalized for pain in Nigeria. Am J Hematol. 2021 Jan;96(1):89-97. doi: 10.1002/ajh.26028. Epub 2020 Nov 20. |
| 15998894 | Background | Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V, Hazen SL, Vichinsky EP, Morris SM Jr, Gladwin MT. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. 2005 Jul 6;294(1):81-90. doi: 10.1001/jama.294.1.81. |
| 23645695 | Background | Morris CR, Kuypers FA, Lavrisha L, Ansari M, Sweeters N, Stewart M, Gildengorin G, Neumayr L, Vichinsky EP. A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes. Haematologica. 2013 Sep;98(9):1375-82. doi: 10.3324/haematol.2013.086637. Epub 2013 May 3. |
| 37064309 | Background | Sadeghi A, Taherifard E, Dehdari Ebrahimi N, Rafiei E, Hadianfard F, Taherifard E. Effects of l-arginine supplementation in patients with sickle cell disease: A systematic review and meta-analysis of clinical trials. Health Sci Rep. 2023 Apr 11;6(4):e1167. doi: 10.1002/hsr2.1167. eCollection 2023 Apr. |
| 33815929 | Background | Onalo R, Cilliers A, Cooper P. Impact of oral L-arginine supplementation on blood pressure dynamics in children with severe sickle cell vaso-occlusive crisis. Am J Cardiovasc Dis. 2021 Feb 15;11(1):136-147. eCollection 2021. |
| 12626350 | Background | Morris CR, Morris SM Jr, Hagar W, Van Warmerdam J, Claster S, Kepka-Lenhart D, Machado L, Kuypers FA, Vichinsky EP. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med. 2003 Jul 1;168(1):63-9. doi: 10.1164/rccm.200208-967OC. Epub 2003 Mar 5. |
| 37587492 | Result | Rees CA, Brousseau DC, Cohen DM, Villella A, Dampier C, Brown K, Campbell A, Chumpitazi CE, Airewele G, Chang T, Denton C, Ellison A, Thompson A, Ahmad F, Bakshi N, Coleman KD, Leibovich S, Leake D, Hatabah D, Wilkinson H, Robinson M, Casper TC, Vichinsky E, Morris CR; SCD Arginine Study Group and PECARN. Sickle Cell Disease Treatment with Arginine Therapy (STArT): study protocol for a phase 3 randomized controlled trial. Trials. 2023 Aug 17;24(1):538. doi: 10.1186/s13063-023-07538-z. |
| 41190764 | Result | Rees CA, Hatabah D, Korman R, Ahmad F, Airewele G, Akinsola B, Alzraikat N, Bakshi N, Brousseau DC, Brown K, Campbell AD, Casper TC, Chang TP, Chumpitazi CE, Cohen D, Coleman KD, Cruz AT, Denton C, Ellison A, Fields ME, Harding M, Leibovich S, Remiker A, Singh NV, Thompson AA, Vichinsky E, Villella A, Wynn B, Dampier C, Morris CR; Pediatric Emergency Care Research Network (PECARN). Hospital Variations in Time-To-Crisis-Resolution Among Children and Adolescents With Sickle Cell Disease. Am J Hematol. 2026 Jan;101(1):206-212. doi: 10.1002/ajh.70129. Epub 2025 Nov 5. |
| 38775255 | Derived | Bolarinwa AB, Oduwole O, Okebe J, Ogbenna AA, Otokiti OE, Olatinwo AT. Antioxidant supplementation for sickle cell disease. Cochrane Database Syst Rev. 2024 May 22;5(5):CD013590. doi: 10.1002/14651858.CD013590.pub2. |
| BG001 | Placebo | Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
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Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
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| Secondary | Total Parenteral Opioid Use | Total parenteral opioid use is assessed as morphine equivalents in milligrams per kilogram (mg/kg). | Posted | Mean | Standard Deviation | milligrams per kilogram (mg/kg) | From the time of IV placement throughout opioid treatment (up to 1,724.1 hours) |
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| Secondary | Change in Pain Score | Pain is assessed using a scale from 0 to 10, where 10 is the highest pain level. Daily highest and lowest pain scores are recorded. The change in score is calculated by subtracting the score at discharge from the score at the time of presentation. | Posted | Mean | Standard Deviation | score on a scale | Time of presentation and on the day of discharge (up to 554.8 days) |
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| Secondary | Change in Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Score | The PROMIS Pain Interference instrument is an 8-item, self-administered survey that assesses the interference of pain on daily activities. Participants are asked to respond to questions regarding the extent of their pain. Responses range from 1 to 5, where 1 represents "not at all" and 5 represents "very much". Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of pain interference compared to the reference population, while scores higher than 50 indicate greater pain interference compared to the reference population. The change in score is calculated by subtracting the score at the time of discharge from the score from within 12 hours of study drug delivery. The change in score is calculated by subtracting the score at discharge from the score within 12 hours of study drug delivery. | Posted | Mean | Standard Deviation | score on a scale | Within 12 hours of study drug delivery, and on the day of discharge (up to 554.8 days) |
|
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| Secondary | Change in PROMIS Pain Behavior Score | The PROMIS Pain Behavior instrument is an 8-item, self-administered survey that assesses external manifestations of pain. Participants are asked to respond to questions regarding the extent of their pain. Responses range from 1 to 5, where 1 represents "never" and 5 represents "always". Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of pain behavior compared to the reference population, while scores higher than 50 indicate greater pain behavior compared to the reference population. The change in score is calculated by subtracting the score at discharge from the score within 12 hours of study drug delivery. | Posted | Mean | Standard Deviation | score on a scale | Within 12 hours of study drug delivery, and on the day of discharge (up to 554.8 days) |
|
|
|
| Secondary | Change in PROMIS Fatigue Score | The PROMIS Fatigue instrument is an 8-item, self-administered survey that assesses fatigue level within the past seven days. Participants are asked to respond to questions regarding fatigue frequency. Responses range from 1 to 5, where 1 represents "never" and five represents "always". Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of fatigue compared to the reference population, while scores higher than 50 indicate greater fatigue compared to the reference population. The change in score is calculated by subtracting the score at discharge from the score within 12 hours of study drug delivery. | Posted | Mean | Standard Deviation | score on a scale | Within 12 hours of study drug delivery and on the day of discharge (up to 554.8 days) |
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| Other Pre-specified | Time-to-crisis Resolution By Sex | The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery. | Data were stratified by sex. | Posted | Mean | Standard Deviation | hours | From study drug delivery to last IV opioid treatment (up to 1,724.1 hours) |
|
|
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| Other Pre-specified | Time-to-crisis Resolution By Race | The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery. | Data were stratified by race. | Posted | Mean | Standard Deviation | hours | From study drug delivery to last IV opioid treatment (up to 1,724.1 hours) |
|
|
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| Other Pre-specified | Time-to-crisis Resolution By Ethnicity | The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery. | Data were stratified by ethnicity. | Posted | Mean | Standard Deviation | hours | From study drug delivery to last IV opioid treatment (up to 1,724.1 hours) |
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| Other Pre-specified | Medication Quantification Score (MQS) | Medication Quantification Score (MQS) is a tool to objectively quantify pain. The MQS is a validated score calculated based off of daily doses of pain related medications (including acetaminophen, aspirin, NSAIDs, and antidepressants). The MQS is a single numeric value for a patient's pain medication profile. This number is used to track pain levels through a treatment course. | Not Posted | Pre-dose and on day of discharge (up to 2 months) | Participants |
| Other Pre-specified | Hospital Length of Stay | Hospital length of stay in days is recorded. | Not Posted | Up to 6 months | Participants |
| Other Pre-specified | Pediatric PROMIS Score | The Pediatric PROMIS assesses five domains of health with in a 35-item instrument. The survey is completed by patients ages 8-17 years of age and parents of children ages 5-17 years of age. The domains included are: pain behavior (8 items), pain interference (8 items), pain intensity (1 item), physical stress experiences (8 items), and fatigue (10 items). Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of the concept being measured compared to the reference population, while scores higher than 50 indicate a greater amount of the concept being measured (e.g., more fatigue) compared to the reference population. | Not Posted | Within 12 hours of study drug delivery and on the day of discharge (up to 2 months) | Participants |
| Other Pre-specified | PedsQL SCD Pain and Hurt Scale Score | The Pain and Hurt scale of the PedsQL SCD module has 9 items asking how much of a problem each item has been during the past month. Responses to items are given on a 5-point Likert scale where 0 = never a problem and 4 = almost always a problem. Items are reversed and transformed to a scale of 0 to 100 then the mean score for the scale is calculated. The total score for the Pain and Hurt scale ranges from 0 to 100 with higher scores indicating greater quality of life and lower SCD symptoms. | Not Posted | Within 12 hours of study drug delivery and on the day of discharge (up to 2 months) | Participants |
| Other Pre-specified | PedsQL SCD Pain Impact Scale Score | The Pain Impact scale of the PedsQL SCD module has 10 items asking how much of a problem each item has been during the past month. Responses to items are given on a 5-point Likert scale where 0 = never a problem and 4 = almost always a problem. Items are reversed and transformed to a scale of 0 to 100 then the mean score for the scale is calculated. The total score for the Pain Impact scale ranges from 0 to 100 with higher scores indicating greater quality of life and lower SCD symptoms. | Not Posted | Within 12 hours of study drug delivery and on the day of discharge (up to 2 months) | Participants |
| Other Pre-specified | Arginine Bioavailability | Peak plasma arginine concentration is assessed via pharmacokinetic study. | Not Posted | Pre-Dose, Day 2, after 21 doses (Day 7 or 8) or at discharge (if discharged prior to Dose 21) | Participants |
| Other Pre-specified | Mitochondrial Function | Mitochondrial respiratory complex activities are measured to estimate mitochondrial function. | Not Posted | Pre-Dose, Day 2, after 21 doses (Day 7 or 8) or at discharge (if discharged prior to Dose 21) | Participants |
| 0 |
| 129 |
| 22 |
| 129 |
| 81 |
| 129 |
| EG001 | Placebo | Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID). | 0 | 142 | 25 | 142 | 83 | 142 |
| Sickle cell anaemia with crisis | General disorders | Non-systematic Assessment |
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| Acidosis | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Acute chest syndrome | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Aspiration | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Asthenia | General disorders | Non-systematic Assessment |
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| Drug dependence | General disorders | Non-systematic Assessment |
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| Gastroenteritis | Gastrointestinal disorders | Non-systematic Assessment |
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| Hallucination | General disorders | Non-systematic Assessment |
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| Intensive care | General disorders | Non-systematic Assessment |
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| Intentional overdose | Psychiatric disorders | Non-systematic Assessment |
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| Limb discomfort | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Pyrexia | General disorders | Non-systematic Assessment |
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| Respiratory distress | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Acute chest syndrome | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Decreased appetite | General disorders | Non-systematic Assessment |
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| Decreased haemoglobin | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Headache | General disorders | Non-systematic Assessment |
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| Hypoxemia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Nausea | General disorders | Non-systematic Assessment |
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| Pyrexia | General disorders | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Transfusion | Blood and lymphatic system disorders | Non-systematic Assessment |
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Not provided
Not provided
Not provided
| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Male |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or not reported |
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| Not Hispanic or Latino |
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| Unknown or not reported |
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