Effect of ketofol on persistent pain in patients with cancer that has spread to the bone

ISRCTN ISRCTN00353297
DOI https://doi.org/10.1186/ISRCTN00353297
Secondary identifying numbers B100IEG0110001
Submission date
08/11/2013
Registration date
21/11/2013
Last edited
13/06/2014
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Intractable (unmanageable) cancer pain is a serious health problem when the cancer spreads to the bone. There are options for relieving cancer pain. Conventional painkillers are usually used according to the principles of the World Health Organization. Cancer patients generally develop tolerance to systemic opioids. As conventional pain relief methods do not always relieve intractable cancer pain, researchers are investigating drugs such as ketamine to increase the effectiveness and to decrease their side effects. Ketamine has been recommended to effectively relieve pain patients with chronic pain. Ketamine can also be used as an painkiller for cancer pain. Some studies suggest that another drug, propofol, has pain relief properties, and it has been used as an adjuvant painkiller. We put forward that giving ketamine plus propofol, known as ketofol, may be effective in patients with intractable cancer pain.

Who can participate?
Patients who had intractable cancer pain caused by the cancer spreading to the bone can participate in this study.

What does the study involve?
The patients were randomly allocated to two groups. The control group received a placebo (dummy) fat emulsion and the ketofol group received ketamine plus propofol into their vein. We recorded age, body measurements, heart rate, blood pressure and pain. These measurements were done at the start of the study and at various intervals for 48 hours.

What are the possible benefits and risks of participating?
Patients in the ketofol group may experience a reduction in pain. The side effects include nausea, vomiting, hallucination, double vision, dreaming and nightmares.

Where is the study run from?
The study is run from Ankara Numune Training and Research Hospital, Ankara, Turkey.

When is study starting and how long is it expected to run for?
The study started in December 2009 and is expected to run for 3 months.

Who is funding the study?
Devrek-Dent Private Health Care Limited Company, Turkey.

Who is the main contact?
Dr Derya Gokcinar
dgokcinar@yahoo.com

Contact information

Dr Derya Gokcinar
Scientific

Yildirim Beyazit Mahallesi, Derman Caddesi, No.17 Kazan, Ankara, Turkey
Ankara
06980
Türkiye

Phone +905052283639
Email dgokcinar@yahoo.com

Study information

Study designProspective double-blind randomized controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please contact kahvecikadriye@gmail.com to request a patient information sheet
Scientific titleThe analgesic effect of ketofol on intractable pain in cancer patients with bone metastasis
Study objectivesIt was hypothesised that Ketofol infusion relieved pain and decreased the supplemental analgesic requirement in patients with intractable cancer pain with bone metastasis. The null hypothesis was that there was no any analgesic effect of ketofol on intractable pain in cancer patients with bone metastasis.

On 13/06/2014 the following changes were made to the trial record:
1. The anticipated start date was changed from 03/12/2012 to 01/12/2009
2. The anticipated end date was changed from 03/07/2013 to 28/02/2010
3. The target number of participants was changed from 85 to 80
Ethics approval(s)Ethics committee of the Turkish Ministry of Health, Ref: B100IEG0110001
Health condition(s) or problem(s) studiedIntractable pain in cancer patients with bone metastasis
InterventionBased on the dosage of ketamine, propofol and ketofol for the sedation and/or analgesia in the previous studies, we conducted a preliminary study on 20 cancer patients with intractable pain to determine the effective analgesic ketofol dose without performing sedation. We found that the dosage of ketofol including ketamine 5µgkg per min and propofol 5µgkg per min could maintain Ramsey Sedation Score at 2 and the VAS pain score < 4 cm in more than 50% of the subjects.
All patients for analgesia was initially provided via titrating morphine in increments of 3 mg every 5 min until the VAS pain score was < 4 cm. Patients were also given access to a PCA device set to deliver 1mg boluses of IV morphine, with a lockout period of 5 min and no background infusion or limits. The PCA regimen was continued for 48 h. The patients were randomly divided into 2 groups. The control group (n = 36) received intravenous 10% fat emulsion (Intralipid® 10%, Fresenius-kabi Turkey Inc., Istanbul, Turkey) 5µgkg per min over 48 h and the ketofol group (n = 36) received Racemic ketamine (Ketalar®, Pfizer Warner Lambert Turkey Inc., Istanbul, Turkey) 5µgkg per min plus propofol (Propofol 1% Fresenius®, Fresenius-kabi Turkey Inc., Istanbul, Turkey) 5µgkg per min over 48 h. Propofol (150 mg) and ketamine (150 mg) were diluted with 0.9% sodium chloride (150 mL); the concentration of both ketamine and propofol was 1 mgml per min.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Ketofol
Primary outcome measure1. VAS scores were recorded at baseline (after first morphine titration), 1 h, 3 h, 6 h, 12 h, 24 h and 48 h
2. Cumulative morphine consumption (CMC) was recorded at 1 h, 3 h, 6 h, 12 h, 24 h and 48 h after the start of the drugs infusion
Secondary outcome measures1. Age, gender, weight, height, underlying disease, length of stay in hospital (LOS) measured at baseline
2. Vital status at hospital was evaluated at one month
3. Simplified acute physiology score III (SAPS III) points, and SAPS III predicted mortality (%) were recorded at baseline
4. Heart rate (HR) and mean arterial pressure (MAP) were recorded by an independent investigator at baseline, 5 min, 15 min, 30 min, 1 h, 3 h, 6 h, 12 h, 24 h and 48 h
5. Side effects including nausea, vomiting, hallucination, double vision, dreaming and nightmares were recorded at 48 hours
Overall study start date01/12/2009
Completion date28/02/2010

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants85
Key inclusion criteria1. Intractable cancer pain caused by bone metastasis
2. Age 18 years or over
3. Recent use of the fentanyl patch
4. Duration of pain being 4 weeks or longer
5. Visual analog scale (VAS) pain intensity score during the previous week ≥ 5 cm (on a scale of 0-10 cm)
Key exclusion criteriaWe excluded the patients with a confirmed or suspected allergy to intravenous fat emulsion, propofol or ketamine
Date of first enrolment01/12/2009
Date of final enrolment28/02/2010

Locations

Countries of recruitment

  • Türkiye

Study participating centre

Yildirim Beyazit Mahallesi, Derman Caddesi, No.17 Kazan, Ankara, Turkey
Ankara
06980
Türkiye

Sponsor information

Devrek-Dent Private Health Care Limited Company (Turkey)
Industry

Irmak sokak, No.12/1
Devrek
Zonguldak
67800
Türkiye

Funders

Funder type

Industry

Devrek-Dent Private Health Care Limited Company (Turkey)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan