Arginine Therapy for Sickle Cell Disease Pain

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02536170
• Other study ID #: IRB00076988
• Secondary ID: FD-R-0048141K24A
• Status: Completed
• Phase: Phase 2
• Start date: February 2016
• Est. completion date: February 21, 2021

Study information

• Verified date: August 2023
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: February 21, 2021
• Est. primary completion date: February 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease
• Vaso-occlusive Pain Episode

Intervention

Drug:
• L-arginine
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.
• L-arginine Loading Dose
One loading dose of L-arginine will be dispensed intravenously (IV) at 200 mg/kg

Other:
• Placebo
Placebo of intravenous (IV) normal saline 1-2 ml/kg three times a day until discharge from the emergency department (ED) or hospital.

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta at Egleston	Atlanta	Georgia
United States	Children's Healthcare of Atlanta at Hugh Spalding	Atlanta	Georgia
United States	Children's Healthcare of Atlanta at Scottish Rite	Atlanta	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Emory University	Children's Healthcare of Atlanta, National Center for Complementary and Integrative Health (NCCIH)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bakshi N, Liu Z, Gillespie S, Keesari R, Leake D, Khemani K, Kumari P, Rees CA, Dampier CD, Morris CR. Patient reported outcomes in children with sickle cell disease at presentation for an acute pain episode. Blood Adv. 2022 Nov 2:bloodadvances.2021006794. doi: 10.1182/bloodadvances.2021006794. Online ahead of print. No abstract available. — View Citation

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 progres — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Rate of Blood Transfusion	Number of participants requiring a blood transfusion throughout the study period.	Duration of study (Up to 8 days)
Secondary	Oxygen Saturation Level	Average oxygen saturation level of participants at time of ED arrival	At time of Emergency Department Admission
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)