Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis

NCT ID: NCT03296345

Last Updated: 2021-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2018-04-30

Brief Summary

Acute vaso-occlusive episodes (VOEs) in sickle cell disease (SCD) are primarily managed with opioids. Tolerance and hyperalgesia to opioids develops due to N-methyl-D-aspartate (NMDA)-receptor mediated activation of the nociceptive system, and as a receptor antagonist, ketamine mitigates this. Intravenous (IV) ketamine has demonstrated efficacy in reducing post-operative, chronic, and cancer-related pain in pediatrics, as well as in reducing time to pain control in the emergency department (ED) in adults. Limited studies suggest efficacy in adult opioid-refractory SCD patients. This study is investigating the safety and tolerability of adjuvant low-dose IV ketamine bolus for pediatric SCD VOE in the ED, as well as its efficacy in improving pain control and reducing hospitalization.

Detailed Description

In this cohort study, all consenting pediatric sickle-cell patients between 10 and 25 years old who were cared for at UCSF Benioff Children's Hospital Oakland (UCSFBCHO) presenting to the emergency department for VOC were enrolled in the study. Patients were compared to themselves in a time series, pre and post exposure to the study intervention (low-dose ketamine bolus at 0.2 mg/kg x 1 prior to second dose of IV opiate). The pediatric FACES pain scale was used to measure pain scales at pre-designated time points in the ED per standard nursing protocol (FACES for younger kids, visual analog scale in adolescents/young adults). Opiate usage was summed in the ED, converted to mg/kg/hour of morphine equivalents (since different opioids agents were given to different patients based on individual historical efficacy, and since length of stay in the emergency room could affect total morphine equivalents received), and compared between the pre and post-intervention groups. In addition, length of stay, time to 50% pain control, presentation and discharge pain scores, and likelihood of discharge from the ED were compared. Data was be collected via chart review in the UCSFBCHO system by study investigators. Pre-intervention data from the past three patient encounters (e.g., the mean of the mg/kg/hour of morphine equivalents used in the last three patient encounters prior to receipt of ketamine) was compared to the post intervention data. In addition, a survey, which is attached, was given to patients/families at the time of the drug administration to attempt to discern if patients subjectively experienced improvement in their pain and if they experienced any negative side effects due to the drug administration. Monitoring for adverse events was recorded for each patient encounter.

Conditions

Sickle Cell Disease; Vaso-Occlusive Crisis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention

Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Pain scores were collected using the FACES scale currently in place. In consenting patients, chart review was performed with the following data collected: mg/kg/hour of morphine equivalents, pain scores on admission, during the encounter, and at discharge, the time to 50% pain reduction, and whether or not the patient was discharged.

In addition, a survey, which is attached, was given to patients/families at the time of drug administration to determine if they experienced a subjective improvement in their pain and if they suffered any undue side effects due to drug administration.

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: DRUG

The intervention is IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs).

Historical Control

Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Ketamine

The intervention is IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs).

Intervention Type: DRUG

Other Intervention Names

Ketalar

Eligibility Criteria

Inclusion Criteria

• All English-speaking, sickle cell patients who receive their care at UCSFBCHO in the Department of Hematology who are 8-to-25-years-old presenting to the emergency department for VOC were asked to enroll.

Exclusion Criteria

• Prior adverse reaction to ketamine
• Patients were asked during the consent process if they have ever received ketamine, and if so, if they had any serious adverse reaction, such as difficulty breathing, dysphoria, hallucinations, or allergic reaction. If they have, ketamine was not given to these patients.
• Patients who have received ketamine and experienced nausea or vomiting will be asked if they wish to receive the medication. If they do not, they did not receive ketamine.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

UCSF Benioff Children's Hospital Oakland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan B Cooper-Sood, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital and Research Center of Oakland

Locations

UCSF Benioff Children's Hospital and Research Center Oakland

Oakland, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23565738 (View on PubMed)

Tawfic QA, Faris AS, Eipe N. Sickle cell pain management: are we missing the role of pronociception and neuropathic pain? Paediatr Anaesth. 2013 Nov;23(11):1104-5. doi: 10.1111/pan.12269. No abstract available.

Reference Type: BACKGROUND

PMID: 24088202 (View on PubMed)

Jennings CA, Bobb BT, Noreika DM, Coyne PJ. Oral ketamine for sickle cell crisis pain refractory to opioids. J Pain Palliat Care Pharmacother. 2013 Jun;27(2):150-4. doi: 10.3109/15360288.2013.788599. Epub 2013 May 21.

Reference Type: BACKGROUND

PMID: 23692261 (View on PubMed)

Zempsky WT, Loiselle KA, Corsi JM, Hagstrom JN. Use of low-dose ketamine infusion for pediatric patients with sickle cell disease-related pain: a case series. Clin J Pain. 2010 Feb;26(2):163-7. doi: 10.1097/AJP.0b013e3181b511ab.

Reference Type: BACKGROUND

PMID: 20090444 (View on PubMed)

Riha H, Aaronson P, Schmidt A. Evaluation of analgesic effects of ketamine through sub-dissociative dosing in the ED. Am J Emerg Med. 2015 Jun;33(6):847-9. doi: 10.1016/j.ajem.2015.03.045. Epub 2015 Mar 25. No abstract available.

Reference Type: BACKGROUND

PMID: 25865160 (View on PubMed)

Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med. 2014 Nov;21(11):1193-202. doi: 10.1111/acem.12510.

Reference Type: BACKGROUND

PMID: 25377395 (View on PubMed)

Drake AB, Milne WK, Carpenter CR. Hot Off the Press: Subdissociative-dose Ketamine for Acute Pain in the Emergency Department. Acad Emerg Med. 2015 Jul;22(7):887-9. doi: 10.1111/acem.12705. Epub 2015 Jun 30. No abstract available.

Reference Type: BACKGROUND

PMID: 26130219 (View on PubMed)

Miller JP, Schauer SG, Ganem VJ, Bebarta VS. Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. Am J Emerg Med. 2015 Mar;33(3):402-8. doi: 10.1016/j.ajem.2014.12.058. Epub 2015 Jan 7.

Reference Type: BACKGROUND

PMID: 25624076 (View on PubMed)

Uprety D, Baber A, Foy M. Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report and review of literature. Ann Hematol. 2014 May;93(5):769-71. doi: 10.1007/s00277-013-1954-3. Epub 2013 Nov 15.

Reference Type: BACKGROUND

PMID: 24232306 (View on PubMed)

Tawfic QA, Faris AS, Kausalya R. The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease. J Pain Symptom Manage. 2014 Feb;47(2):334-40. doi: 10.1016/j.jpainsymman.2013.03.012. Epub 2013 Jul 12.

Reference Type: BACKGROUND

PMID: 23856095 (View on PubMed)

Ahern TL, Herring AA, Anderson ES, Madia VA, Fahimi J, Frazee BW. The first 500: initial experience with widespread use of low-dose ketamine for acute pain management in the ED. Am J Emerg Med. 2015 Feb;33(2):197-201. doi: 10.1016/j.ajem.2014.11.010. Epub 2014 Nov 15.

Reference Type: BACKGROUND

PMID: 25488336 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2010-010

Identifier Type: -

Identifier Source: org_study_id