Arginine Therapy for Sickle Cell Disease Pain

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 2 Randomized Control Trial of Arginine Therapy for Pediatric Sickle Cell Disease Pain

Conditions
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Sickle Cell Disease, Vaso-occlusive Pain Episode

Intervention / Treatment
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* Drug: L-arginine
* Drug: L-arginine Loading Dose
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

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: L-Arginine<br>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. | Drug: L-arginine<br>* 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.<br>* Other names: Arginine;|
| Experimental: Loading Dose and L-Arginine<br>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. | Drug: L-arginine<br>* 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.<br>* Other names: Arginine;Drug: L-arginine Loading Dose<br>* One loading dose of L-arginine will be dispensed intravenously (IV) at 200 mg/kg<br>* Other names: Arginine;|
| Placebo Comparator: Placebo<br>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. | Other: Placebo<br>* Placebo of intravenous (IV) normal saline 1-2 ml/kg three times a day until discharge from the emergency department (ED) or hospital.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Post study drug delivery to discharge from the hospital (Up to 8 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Hospital Stay | The total number of hours spent in the hospital from study drug delivery to time of discharge. | Discharge (Up to 8 days) | 
| 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. | Post study drug delivery (Up to 8 hours) | 
| 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 | Post study drug delivery until discharge (up to 8 days) | 
| 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). | Baseline, Time of discharge (Up to 8 days) | 
| Length of Emergency Department (ED) Stay | Total hours from time of ED triage to ED discharge or hospital admission. | Until discharge or Hospital Admission (Up to 24 hours) | 
| Rate of Emergency Department (ED) Discharge | Number of participants discharged from ED without a hospital ward admission. | Post emergency department admission (Up to 24 hours) | 
| 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) | Post 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. | Duration of study (Up to 8 days) | 
| Rate of Acute Chest Syndrome | Number of participants who develop acute chest syndrome (not diagnosed prior to study drug delivery) throughout the study period. | Duration of study (Up to 8 days) | 
| Rate of Blood Transfusion | Number of participants requiring a blood transfusion throughout the study period. | Duration of study (Up to 8 days) | 
| Oxygen Saturation Level | Average oxygen saturation level of participants at time of ED arrival | At time of Emergency Department Admission | 
| Oxygen Saturation Level | The difference in oxygen saturation levels from emergency department arrival to hospital discharge. | At time of hospital admission and at time of Hospital discharge (Up to 8 days) | 
| 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. | Post hospital discharge (within 72 hours) | 
| Rate of Hospital Re-admissions Within 72 Hours | Number of patients readmitted to the hospital within 72 hours of discharge. | Post hospital discharge (within 72 hours) | 
| 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. | Post hospital discharge (within 30 days) | 
| Rate of Hospital Re-admissions With 30 Days | Number of patients readmitted to the hospital within 30 days of discharge. | Post hospital discharge (within 30 days) | 

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