Low-dose Ketamine vs Morphine for Vaso-occlusive Crisis in Sicklers

Acute Pain Clinical Trial

— KEM-VOC  

Official title:

Low-dose Ketamine Versus Morphine for Severe Painful Sickle Cell Crises in Children at Mulago Hospital: A Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02434939
• Other study ID #: 2013/HD07/606U
• Status: Completed
• Phase: Phase 4
• First received: April 22, 2015
• Last updated: February 12, 2016
• Start date: June 2015
• Est. completion date: February 2016

Study information

• Verified date: July 2015
• Source: Makerere University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Uganda: National Drug AuthorityUganda: National Council for Science and Technology
• Study type: Interventional

Clinical Trial Summary

This clinical trial will inform of the role of Low dose ketamine in the acute treatment of severe painful sickle cell crisis in children in a day-case sickle cell centre. The primary aim is to determine whether Low dose ketamine is non inferior to morphine in the management of acute painful sickle cell crises. The specific objectives will be to determine the maximal change in NRS pain score following administration of ketamine and to examine the safety profile of ketamine compared to morphine in this population.

The investigators hypothesize that low dose ketamine will result in similar effective pain control as morphine alone and will not be associated with an increase in adverse events.

Description:

Acute pain episodes associated with sickle cell disease (SCD) are very difficult to manage effectively. Opioid, phobia, tolerance, availability and side effects have been major roadblocks in our ability to provide these patients with adequate pain relief.

Ketamine is cheap, widely safe, readily available drug in low-middle income setting, with analgesic effects at sub-anesthetic doses and has a wide range of use including surgery (opioid sparing drug), burns (change of dressing ) and cancer related pain. However literature concerning its use in sickle cell crises is still limited in our setting.

This is a double-blinded, randomized control, study comparing low-dose ketamine (LDK) to morphine for acute pain control in children with sickle cell crises. A sample of 240 children will be enrolled from a population of patients with Sickle Cell Anemia aged 7-18 who present to the Mulago Referral Hospital Sickle Cell Clinic with acute painful Vaso-occlusive Crisis (VOC). To take part in the study, a patient must have a pain score of 7 and above as assessment by the treating physician in addition to the patient meeting all other study criteria.

After enrollment, the consented patient's weight in kg will be determined at the holding area with a standardized calibrated weighing scale (SECA - From National Medical Stores, Uganda) before transfer to the treatment room.

Baseline clinical parameters which include pulse rate, respiratory rate, blood pressure, temperature, oxygen saturation, level of consciousness, Numerical Rating Scale (NRS) Pain score (with 0 being no pain and 10 being the worst pain possible) and sites of VOC pain will be noted.

This will be followed by placement of a peripheral intravenous cannula, G22-G20 (this is part of standard care) with subsequent fluid load of 15mls per kg of crystalloid, repeated if required. Other non analgesic therapies will be prescribed by the primary care provider and started concurrently.

The recruited patients will then be randomized and allocated to receive Ketamine at 1mg/kg (study drug) or morphine at 0.1mg/kg (active control) through an intravenous infusion using a syringe pump(Agilia, Fresenius Kabi) over 5minutes.

The vital signs and NRS and Ramsay sedation scores (RSS) will be reassessed and recorded at 5, 10 and 20 minutes after the end of the drug infusion. However, patient monitoring will be continuous. At 20 minutes, patients with NRS of 5 and more will be given a second dose without crossing over. Monitoring will be continued as above. If the NRS is less than 5, they will continue to be reassessed every 20 minutes (vital signs, NRS, RSS and adverse events) until either inpatient admission to the ward or up to 120 minutes after which they will be cared for by the ward team..

If they require a third dose of pain medication at any time during the study, this will be deemed as treatment failure and the treating pediatrician will be contacted to provide further pain control.

Any Ketamine (even for morphine) side effects as listed in the risks and safety section will monitored for among the study subjects and will treated by the study team.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: February 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Years to 18 Years

Eligibility

Inclusion Criteria:

• Children aged 7-18 years

• sickle cell anemia patient with severe acute painful crisis

• Parental consent and child assent where applicable

Exclusion Criteria:

• Oxygen saturations below 90% on initial assessment

• Altered conscious and mental state that hinders communication

• Current enrollment in another clinical trial involving an investigational drug.

• History of a stroke

• Hypertension,

• Increased intracranial pressure.

• Glaucoma,

• Failed/ Difficult IV access

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Pain
• Sickle Cell Crisis

Intervention

Drug:
• Low dose ketamine
Children in this arm shall receive a slow infusion of ketamine at a sub-anesthetic dose and monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
• Morphine
Children in this arm shall receive intravenous infusion of morphine at analgesic dose and then monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.

Locations

Country	Name	City	State
Uganda	Sickle Cell clinic, Mulago Hospital Complex	Kampala

Sponsors (1)

Lead Sponsor	Collaborator
Makerere University

Country where clinical trial is conducted

Uganda, 

References & Publications (1)

Marcus RJ, Victoria BA, Rushman SC, Thompson JP. Comparison of ketamine and morphine for analgesia after tonsillectomy in children. Br J Anaesth. 2000 Jun;84(6):739-42. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal change in NRS pain scores as a percentage of baseline NRS pain score.	Evaluation of the maximal change in patient's pain (based on their numerical rating scale score) throughout the study versus their initial pain rating prior to drug administration.	5, 10, 20, 40, 60, 80, 100, 120 minutes post drug adminstration	No
Secondary	Time to maximal analgesic effect and duration of action of ketamine	Following dosage with study medication, the amount of time taken to demonstrate the maximal change in the patient's NRS pain score.; Maximal change in NRS pain score is to be defined as the largest change from patient's baseline pain score. Duration of maximal change is how long the patient's pain score remained at this level.	5, 10, 20, 40, 60, 80, 100, 120 minutes post drug administration	No
Secondary	Incidence of side effects, including outlying vital signs	The patient will be assessed for vital signs (blood pressure, heart rate, respiratory rate, oxygen saturation), Numerical Rating Score (NRS) and Ramsay Sedation Scale (RSS) score at 5,10,20 minutes following medication administration and then every 20 minutes until a total of 120 minutes from the first dose of study medication. All side effects and outlying vital signs will be documented.	5, 10, 20, 40, 60, 80, 100, 120 minutes post drug administration	No
Secondary	Incidence of treatment failure with ketamine.	Requiring more than two doses of the study medication provided for adequate pain control	120 minutes	No