Sickle Cell CrisisPhase 4KEM-VOCNCT02434939
Low-dose Ketamine vs Morphine for Vaso-occlusive Crisis in Sicklers
A Phase 4 study testing Low dose ketamine and Morphine in people with Sickle Cell Crisis and Acute Pain, run by Makerere University at 1 site in Uganda.
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. Read more about this study
- Who is it for?
- Ages 7 to 18 years
- Conditions the study is for
- Sickle Cell Crisis, Acute Pain
- What is being tested?
- Low dose ketamine and Morphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteUganda
- Study dates
- Jun 2015to Feb 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children aged 7-18 years
- sickle cell anemia patient with severe acute painful crisis
- Parental consent and child assent where applicable
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Low-dose Ketamine Versus Morphine for Severe Painful Sickle Cell Crises in Children at Mulago Hospital: A Randomised Controlled Trial
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.
Read the 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
- Being tested
- Low dose ketamine, Morphine
- Medical subject headings
- Vaso-Occlusive Crises, Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low dose ketamineDrug
Also called Ketamine hydrochrolide 50mg/ml,Nirma Pharmaceuticals (India)
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.
MorphineDrug
Also called Morphine sulphate 10mg/ml, Martindale Pharmaceuticals (UK)
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.
| Study group | Role | What they receive |
|---|---|---|
| Low dose ketamine | Experimental | 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. Receives: Drug: Low dose ketamine |
| Morphine | Active comparator | 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. Receives: Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal Change in NRS Pain Scores as a Percentage of Baseline NRS Pain Score.
Our primary outcome measurement was the maximum change on the verbal NRS pain scale compared with their initial score (baseline). The NRS was used to measure a patient's subjective level of pain on a scale from 0 (representing no pain at all) to 10 (the worst pain imaginable) using whole numbers. The NRS score was documented just prior to the administration of the study drug (time zero). After infusion of the study drug was complete, NRS scores were documented at 5, 10, 20, and then every 20 minutes thereafter up to 120 minutes. We stopped recording NRS scores prior to 120 minutes if the patient requested a third dose of the study drug, withdrew consent or developed a severe adverse effect.
Measured: 5, 10, 20,25,30, 40,45,50 60, 80, 100, 120 minutes post drug adminstration
Secondary outcomes (3)
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.
Measured: 5, 10, 20, 40, 60, 80, 100, 120 minutes post drug administration
Incidence of Side Effects, Including Outlying Vital Signs
The patient will be assessed for vital signs (blood pressure, heart rate, respiratory rate, oxygen saturation), 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. outlying vital signs recorded.( systolic Blood pressure less than 90mmHg or greater than 150mmHg, Heart rate less than 50bpm or greater than 150bpm, oxygen saturation below 90%, respiratory rate below 9breaths/minute or greater than 40breaths/minute and RSS of 1 or greater than 3) The RSS was used to asses the level of agitation or sedation caused by the intervention .the scale ranges from 1(anxious/agitated) to 6( no response to stimulus-deep sedation) with 2 being the optimal (cooperative, oriented and tranquil).A checklist for side effects like airway problems, allergic reactions, salivation, dysphoria,nystagmus, respiratory/cardiac arrest, awakening hallucinations, nausea/vomiting was used
Measured: 5, 10, 20, 40, 60, 80, 100, 120 minutes post drug administration
Incidence of Treatment Failure by Treatment Group.
Requiring more than two doses of the study medication provided for adequate pain control
Measured: 120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2015 (estimated)
- Study startJun 2015
- Primary completionJan 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell CrisisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- Makerere University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Felix A. Lubega, MBChB, Principal investigator, Makerere University, College of Health Sciences, Department of Anesthesia and Critical CareTonny S. Luggya, MMed, Study chair, Makerere University, College of Health Sciences, Department of Anaesthesia and Critical careDeogratias Munube, MMed, Study director, Makerere University, College of Health Sciences, Department of Child Health and PediatricsFred Bulamba, MBChB, Study director, Makerere University, College of Health Sciences, Department of Anaesthesia and Critical careMithrika S De Silva, MD, Study director, University of Sydney, Department of Peadiatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02434939
- Sponsor's protocol ID
- 2013/HD07/606U
- Acronym
- KEM-VOC
- Status last verified
- Jun 2016
- First submitted
- 22 Apr 2015
- Last updated
- 3 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 10895748Lubega 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.
PubMed 29794277
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-dose Ketamine Versus Morphine for Severe Painful Sickle Cell Crises in Children at Mulago Hospital: A Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT02434939
- Acronym / sponsor ID
- KEM-VOC / 2013/HD07/606U
- Conditions
- Sickle Cell Crisis, Acute Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- Makerere UniversityUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Jan 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 6 May 2015 (estimated)
- Results
- Posted 3 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low dose ketamine | Experimental | Drug: Low dose ketamineLow 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. |
| Morphine | Active comparator | Drug: MorphineMorphine 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. |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Children aged 7-18 years
- sickle cell anemia patient with severe acute painful crisis
- Parental consent and child assent where applicable
Key exclusion criteria (8 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low dose ketamineAlso: Ketamine hydrochrolide 50mg/ml,Nirma Pharmaceuticals (India)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. | Drug | Low dose ketamine |
| MorphineAlso: Morphine sulphate 10mg/ml, Martindale Pharmaceuticals (UK)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. | Drug | Morphine |
Primary outcome
Maximal Change in NRS Pain Scores as a Percentage of Baseline NRS Pain Score.
Time frame: 5, 10, 20,25,30, 40,45,50 60, 80, 100, 120 minutes post drug adminstration
Our primary outcome measurement was the maximum change on the verbal NRS pain scale compared with their initial score (baseline). The NRS was used to measure a patient's subjective level of pain on a scale from 0 (representing no pain at all) to 10 (the worst pain imaginable) using whole numbers. The NRS score was documented just prior to the administration of the study drug (time zero). After infusion of the study drug was complete, NRS scores were documented at 5, 10, 20, and then every 20 minutes thereafter up to 120 minutes. We stopped recording NRS scores prior to 120 minutes if the patient requested a third dose of the study drug, withdrew consent or developed a severe adverse effect.
3 secondary outcomes
Time to Maximal Analgesic Effect and Duration of Action of Ketamine
Time frame: 5, 10, 20, 40, 60, 80, 100, 120 minutes post drug administration
Incidence of Side Effects, Including Outlying Vital Signs
Time frame: 5, 10, 20, 40, 60, 80, 100, 120 minutes post drug administration
Incidence of Treatment Failure by Treatment Group.
Time frame: 120 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10895748Marcus 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.
- Derived from this study: PubMed 29794277Lubega 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Felix A. Lubega, MBChB principal investigator
Makerere University, College of Health Sciences, Department of Anesthesia and Critical Care
Tonny S. Luggya, MMed study chair
Makerere University, College of Health Sciences, Department of Anaesthesia and Critical care
Deogratias Munube, MMed study director
Makerere University, College of Health Sciences, Department of Child Health and Pediatrics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Low dose ketamine and Morphine in people with Sickle Cell Crisis and Acute Pain, run by Makerere University at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal Change in NRS Pain Scores as a Percentage of Baseline NRS Pain Score. (time frame: 5, 10, 20,25,30, 40,45,50 60, 80, 100, 120 minutes post drug adminstration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02434939, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2016.