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

NCT ID: NCT02434939

Last Updated: 2016-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2016-02-29

Brief 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.

Detailed 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 10 minutes.

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.

Conditions

Sickle Cell Crisis; Acute Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Low dose ketamine

Low dose ketamine 1mg/kg given as an IV infusion via syringe pump over 10 minutes. Maximum of 2 doses to be given during study period that will last 2 hours.

Group Type: EXPERIMENTAL

Low dose ketamine

Intervention Type: DRUG

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

Morphine 0.1mg/kg given as an IV infusion via a syringe pump over 10 minutes. Maximum of 2 doses to be given during the study period that will last 2 hours.

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Ketamine hydrochrolide 50mg/ml,Nirma Pharmaceuticals (India); Morphine sulphate 10mg/ml, Martindale Pharmaceuticals (UK)

Eligibility Criteria

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

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Makerere University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Felix A. Lubega, MBChB

Role: PRINCIPAL_INVESTIGATOR

Makerere University, College of Health Sciences, Department of Anesthesia and Critical Care

Tonny S. Luggya, MMed

Role: STUDY_CHAIR

Makerere University, College of Health Sciences, Department of Anaesthesia and Critical care

Deogratias Munube, MMed

Role: STUDY_DIRECTOR

Makerere University, College of Health Sciences, Department of Child Health and Pediatrics

Fred Bulamba, MBChB

Role: STUDY_DIRECTOR

Makerere University, College of Health Sciences, Department of Anaesthesia and Critical care

Mithrika S De Silva, MD

Role: STUDY_DIRECTOR

University of Sydney, Department of Peadiatrics

Locations

Sickle Cell clinic, Mulago Hospital Complex

Kampala, , Uganda

Countries

Uganda

References

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. doi: 10.1093/oxfordjournals.bja.a013585.

Reference Type: BACKGROUND

PMID: 10895748 (View on PubMed)

Lubega FA, DeSilva MS, Munube D, Nkwine R, Tumukunde J, Agaba PK, Nabukenya MT, Bulamba F, Luggya TS. Low dose ketamine versus morphine for acute severe vaso occlusive pain in children: a randomized controlled trial. Scand J Pain. 2018 Jan 26;18(1):19-27. doi: 10.1515/sjpain-2017-0140.

Reference Type: DERIVED

PMID: 29794277 (View on PubMed)

Other Identifiers

2013/HD07/606U

Identifier Type: -

Identifier Source: org_study_id