Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial

Study Overview
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Brief Summary
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The trial of IV arginine therapy in children with Vaso-occlusive painful episodes (VOE) in sickle cell disease (SCD) is designed to further knowledge on efficacy and safety of the therapy.

Detailed Description
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The trial is designed as a double-blind, placebo controlled, randomized, phase 3, multi-center trial of IV arginine therapy in children with Vaso-occlusive painful episodes (VOE) in sickle cell disease (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 (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.

Official Title
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Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Arginine Hydrochloride
* Other: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 3-21 years of age, inclusive; AND Established diagnosis of sickle cell disease (any genotype); AND Pain requiring medical care in an acute care setting (ED, hospital ward, day hospital, clinic) not attributable to non-sickle cell causes, treated with parenteral opioids. Exclusion Criteria: Responds to 2 doses of IV opioids sufficiently for outpatient management Greater than 12 hours from first dose of intravenous opioids to treat current pain in acute care setting Hemoglobin less than 5 gm/dL or emergent need for red blood cell transfusion for hemodynamically unstable patient; OR Ketamine use in the emergency department for treatment of VOE; OR Glutamine within 30 days; OR New SCD drug use < 3 months (e.g. Hydroxyurea, voxelotor, crizanlizumab, etc) OR Acute mental status or neurological changes; OR Acute stroke or clinical concern for stroke; OR Three or more ED visits for sickle cell related pain receiving parenteral opioids in previous 7 days (not including current ED visit); OR Hospital discharge within previous 7 days; OR Hypotension requiring clinical intervention; hemodynamic instability; septic shock; OR Previous randomization in this arginine phase 3 RCT; OR Use of inhaled nitric oxide, sildenafil or arginine within the last month; OR Non-English or non-Spanish speaking; OR pregnancy; OR Allergy to arginine; OR PI/clinical team concerns for compliance/issues that may adversely impact study participation/outcome; OR Adults 18 years or older who lack medical decision-making capacity to consent

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arginine Hydrochloride<br>Arginine is a nutritional supplement in parenteral form | Drug: Arginine Hydrochloride<br>* One-time L-arginine loading dose (200 mg/kg IV) + standard dose (100 mg/kg IV TID)<br>|
| Placebo Comparator: Placebo<br>Normal saline | Other: Normal saline<br>* Placebo (normal saline) loading dose (2ml/kg IV) + 1ml/kg IV TID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in time-to-crisis resolution | Time in hours from study drug delivery to time of last dose of parenteral opioid delivery | Date and time of first study drug administration and last IV opioid treatment - up to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total parenteral opioid use | Total parenteral opioid use (morphine equivalents, mg/kg) | Time of IV placement, opioid monitoring up to 2 months | 
| Change in pain scores | Daily highest and lowest pain scores will be recorded. 0-10 scale, 10 is strongest pain | Time of IV placement, and on the day of discharge up to 2 months | 
| Change in PROMIS Pain Interference score | PROMIS: pain Interference (8 items). PROMIS measures are scored on the T-score metric. High scores mean more of the concept being measured (e.g., more pain). | Within 12 hours of study drug delivery, and on the day of discharge up to 2 months | 
| Change in PROMIS Pain Behavior score | PROMIS: pain behavior (8 items). PROMIS measures are scored on the T-score metric. High scores mean more of the concept being measured (e.g., more pain) | Within 12 hours of study drug delivery, and on the day of discharge up to 2 months | 
| Change in PROMIS Fatigue score | PROMIS: fatigue (8 items). PROMIS measures are scored on the T-score metric. High scores mean more of the concept being measured (e.g., more fatigue). | Within 12 hours of study drug delivery, and on the day of discharge up to 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arginine Therapy, Pain management