Ketamine Sickle Cell Disease

NCT03502421 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: Pro00033576
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

SC Disease; Pain, Chronic

Keywords

Ketamine

Outcome Measures

Primary Outcomes (2)

• Total opioid Use in milligrams morphine equivalents

  Total opioid Use in milligrams morphine equivalents

  1-3 hours

• Pain scores measured on the Visual Analog Scale 0 - 10

  Pain scores measured on the Visual Analog Scale 0 - 10

  1-3 hours

Secondary Outcomes (3)

• Cost of pharmacotherapy

  1 day

• Length of hospital stay

  1-7 days

• Nausea and vomiting scores Visual Analog Scale 0 - 10

  1-3 hours

Study Arms (2)

Ketamine

EXPERIMENTAL

Continuous infusion of Ketamine 0.3 to 0.5 mg/kg per hour PCA Dilaudid 2.0-2.5 mg

Drug: Ketamine

Opioid Only

NO INTERVENTION

Patient-controlled analgesia Dilaudid 2.0-2.5 mg

Interventions

Ketamine DRUG

Low dose continuous infusion of ketamine 0.3 to 0.5 mg/kg per hour

Ketamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects diagnosed with sickle cell anemia
• Adults aged 18 and older
• Subjects who have given written consent

You may not qualify if:

• 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

Sponsors & Collaborators

• University of South Florida: lead

Related Publications (5)

• 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.

  PMID: 28853040 BACKGROUND

• 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.

  PMID: 23565738 BACKGROUND

• Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006 Aug;60(7):341-8. doi: 10.1016/j.biopha.2006.06.021. Epub 2006 Jul 5.

  PMID: 16854557 BACKGROUND

• Aguado D, Abreu M, Benito J, Garcia-Fernandez J, Gomez 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.

  PMID: 21778336 BACKGROUND

• 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.

  PMID: 27599837 BACKGROUND

MeSH Terms

Conditions

Hemoglobin SC Disease; Chronic Pain

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Anemia, Sickle Cell; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Enrico Camporesi, MD

  University of South Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Controlled Prospective Clinical Trial

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: April 18, 2018
• Study Start: September 1, 2018
• Primary Completion: September 1, 2019
• Study Completion: November 1, 2019
• Last Updated: September 26, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share