Low-dose Ketamine vs Morphine for Vaso-occlusive Crisis in Sicklers
Condition: Sickle Cell Crisis; Acute Pain
MeSH terms: Acute Pain
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Low dose ketamine; Morphine
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Ketamine hydrochrolide 50mg/ml,Nirma Pharmaceuticals (India); Morphine sulphate 10mg/ml, Martindale Pharmaceuticals (UK)
Intervention MeSH terms: Ketamine; Morphine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment