Arginine Therapy for Sickle Cell Disease Pain

Phase 2

Completed

Conditions: Sickle Cell Disease
Vaso-occlusive Pain Episode

Interventions: Other: Placebo
Drug: L-arginine
Drug: L-arginine Loading Dose

Registration Number: NCT02536170

Lead Sponsor: Emory University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 108

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Loading Dose and L-Arginine	L-arginine Loading Dose	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.
Placebo	Placebo	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.
Loading Dose and L-Arginine	L-arginine	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.
L-Arginine	L-arginine	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.

Primary Outcome Measures

Name	Time	Method
Total Parenteral Opioid Use in IV Morphine Equivalents	Post study drug delivery to discharge from the hospital (Up to 8 days)	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

Name	Time	Method
Rate of Blood Transfusion	Duration of study (Up to 8 days)	Number of participants requiring a blood transfusion throughout the study period.
Rate of Return Visits to Emergency Department (ED) Within 30 Days	Post hospital discharge (within 30 days)	Number of ED visits from patients who have been discharged within the previous 30 days.
Total Opioid Dose (ORAL + Parenteral) in mg/kg IV Morphine Equivalents	Post study drug delivery up to hospital discharge (Up to 8 days)	Total opioid dose (ORAL + Parenteral) in mg/kg IV morphine equivalents after study drug delivery up to hospital discharge (up to 8 days)
Rate of Emergency Department (ED) Discharge	Post emergency department admission (Up to 24 hours)	Number of participants discharged from ED without a hospital ward admission.
Time to Vaso-occlusive Pain Event (VOE) Resolution in Emergency Department	Post study drug delivery (Up to 8 hours)	The total number of hours between study drug delivery and the last parenteral opioid.
Total Number of Study Drug Doses	Duration of study (Up to 8 days)	The total number of study drug doses given throughout the study period.
Rate of Acute Chest Syndrome	Duration of study (Up to 8 days)	Number of participants who develop acute chest syndrome (not diagnosed prior to study drug delivery) throughout the study period.
Rate of Return Visits to Emergency Department (ED) Within 72 Hours	Post hospital discharge (within 72 hours)	Number of ED visits from patients who have been discharged within the previous 72 hours.
Rate of Hospital Re-admissions With 30 Days	Post hospital discharge (within 30 days)	Number of patients readmitted to the hospital within 30 days of discharge.
Rate of Hospital Re-admissions Within 72 Hours	Post hospital discharge (within 72 hours)	Number of patients readmitted to the hospital within 72 hours of discharge.
Time to Vaso-occlusive Pain Event (VOE) Resolution in Hospital	Post study drug delivery until discharge (up to 8 days)	The total number of hours between study drug delivery and time of last parenteral opioid use, pain relief improved to tolerate oral pain medications
Oxygen Saturation Level	At time of hospital admission and at time of Hospital discharge (Up to 8 days)	The difference in oxygen saturation levels from emergency department arrival to hospital discharge.
Length of Hospital Stay	Discharge (Up to 8 days)	The total number of hours spent in the hospital from study drug delivery to time of discharge.
Change in Vaso-occlusive Pain (VOE) Scores	Baseline, Time of discharge (Up to 8 days)	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	Until discharge or Hospital Admission (Up to 24 hours)	Total hours from time of ED triage to ED discharge or hospital admission.

Trial Locations

Locations (3): Children's Healthcare of Atlanta at Hugh Spalding
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Atlanta, Georgia, United States
Children's Healthcare of Atlanta at Scottish Rite
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Atlanta, Georgia, United States
Children's Healthcare of Atlanta at Egleston
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Atlanta, Georgia, United States