Arginine Therapy for Sickle Cell Disease Pain

Emory University

Status and phase: Completed; Phase 2

Conditions: Sickle Cell Disease; Vaso-occlusive Pain Episode

Treatments: Other: Placebo; Drug: L-arginine Loading Dose; Drug: L-arginine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02536170

1K24AT009893-01 (U.S. NIH Grant/Contract)

FD-R-004814 (Other Grant/Funding Number)

IRB00076988

Details and patient eligibility

About

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.

Full 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.

Enrollment: 108 patients

Sex: All

Ages: 3 to 21 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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108 participants in 3 patient groups, including a placebo group

L-Arginine

Experimental group

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.

Treatment:

Drug: L-arginine

Loading Dose and L-Arginine

Experimental group

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.

Treatment:

Drug: L-arginine

Drug: L-arginine Loading Dose

Placebo

Placebo Comparator group

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.

Treatment:

Other: Placebo