Ketamine Sickle Cell Disease

Pain, Chronic Clinical Trial

— SCD  

Official title:

A Randomized Controlled Trial to Determine the Efficacy of Ketamine as an Adjunct for Pain Management in Patients With Sickle Cell Crisis

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03502421
• Other study ID #: Pro00033576
• Status: Withdrawn
• Phase: Phase 3
• Start date: September 1, 2018
• Est. completion date: November 1, 2019

Study information

• Verified date: April 2018
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sickle cell disease (SCD) often results in acute vaso-occlusive crisis (VOC), an obstruction of blood vessels resulting in ischemic injury and pain. The pain experienced during these episodes is due to a wide range of pathophysiological processes. Though recent studies have begun to unravel the underlying mechanisms of these processes, literature focused on pain management for sickle cell disease is scarce. Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) remain the predominate treatment for VOC.

However, the efficacy of these treatments has come into question. A large sub-set of patients with SCD report continued pain despite treatment with opioids. Tolerance and opioid-induced hyperalgesia (OIH) may be responsible for unresponsiveness to opioid-centric treatment modalities. New classes of drugs are being tested to prevent and treat acute pain associated with SCD, but in the meantime physicians are looking to existing therapies to bridge the gap.

The N-methyl-d-aspartate (NMDA) receptor has been implicated in both tolerance and OIH. As a NMDA receptor agonist, ketamine has been shown to modulate opioid tolerance and OIH in animal models and clinical settings. Ketamine utilized as a low dose continuous infusion could benefit patients with SCD related pain that are unresponsive to opioid analgesics. Based on limited studies of adjuvant ketamine use for pain management, low-dose ketamine continuous infusion appears safe. Further clinical investigations are warranted to fully support the use of low-dose ketamine infusion in patients with SCD-related pain.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 1, 2019
• Est. primary completion date: September 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects diagnosed with sickle cell anemia

• Adults aged 18 and older

• Subjects who have given written consent

Exclusion Criteria:

• Subjects who are pregnant

• Subjects younger than 18 years

• Subjects known or suspected to have an allergy to opiates/opioids, muscle relaxants or other similar medications

• Subjects who have a contraindication to ketamine

Related Conditions & MeSH terms

• Chronic Pain
• Hemoglobin SC Disease
• Pain, Chronic
• SC Disease

Intervention

Drug:
• Ketamine
Low dose continuous infusion of ketamine 0.3 to 0.5 mg/kg per hour

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of South Florida

References & Publications (5)

Aguado D, Abreu M, Benito J, García-Fernández J, Gómez de Segura IA. Ketamine and remifentanil interactions on the sevoflurane minimum alveolar concentration and acute opioid tolerance in the rat. Anesth Analg. 2011 Sep;113(3):505-12. doi: 10.1213/ANE.0b013e318227517a. Epub 2011 Jul 21. — View Citation

Neri CM, Pestieau SR, Darbari DS. Low-dose ketamine as a potential adjuvant therapy for painful vaso-occlusive crises in sickle cell disease. Paediatr Anaesth. 2013 Aug;23(8):684-9. doi: 10.1111/pan.12172. Epub 2013 Apr 9. Review. — View Citation

Puri L, Nottage KA, Hankins JS, Anghelescu DL. State of the Art Management of Acute Vaso-occlusive Pain in Sickle Cell Disease. Paediatr Drugs. 2018 Feb;20(1):29-42. doi: 10.1007/s40272-017-0263-z. Review. — View Citation

Sun J, Lin H, Feng X, Dong J, Ansong E, Xu X. A comparison of intrathecal magnesium and ketamine in attenuating remifentanil-induced hyperalgesia in rats. BMC Anesthesiol. 2016 Sep 6;16(1):74. doi: 10.1186/s12871-016-0235-9. — View Citation

Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006 Aug;60(7):341-8. Epub 2006 Jul 5. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total opioid Use in milligrams morphine equivalents	Total opioid Use in milligrams morphine equivalents	1-3 hours
Primary	Pain scores measured on the Visual Analog Scale 0 - 10	Pain scores measured on the Visual Analog Scale 0 - 10	1-3 hours
Secondary	Cost of pharmacotherapy	monetary cost of intervention used	1 day
Secondary	Length of hospital stay	Length of stay in the hospital	1-7 days
Secondary	Nausea and vomiting scores Visual Analog Scale 0 - 10	Nausea and vomiting scores Visual Analog Scale 0 - 10	1-3 hours