Clinical trial NCT03431285
Conditions: Sickle Cell Crisis
Sponsor: Imam Abdulrahman Bin Faisal University
Start date: 2018-01-01; Completion date: 2019-02-01
Enrollment: 278 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Investigators hypothesize that administration of ketamine for pain relief in sickle cell patients with vaso-occlusive crisis early on will lead to a more rapid improvement in pain score and less narcotic requirement.

Detailed description:
Sickle cell disease is an inherited hematological disorder where the shape of red blood cells (RBC) is altered into a sickle-like cells resulting in red blood cell destruction and therefore anemia and other complications. It's a widely spread condition in African American population as well as the Southern and Eastern Provinces of Arabian Peninsula.

Acute painful episodes are a very common complication of the disease process, mainly thought to be a result of tissue ischemia due to occlusion of the microcirculation with clusters of sickled RBC(1). This usually involves long bones or spine but can involve other areas. Acute painful crises can also be precipitated by cold exposure, dehydration, infection, hypoxia, acidosis, hypercarbia, or in some cases it is not related to a specific trigger. This condition puts the patient in severe pain requiring multiple Emergency Department (ED) visits and sometimes admission to the hospital. Currently the mainstay of therapy for acute painful crises is hydration and IV analgesia (2). This makes pain control challenging for the emergency physician as management of acute painful crises requires multiple doses of intravenous (IV) opioids. A retrospective study of 19 patients and 57 visits showed that accumulative dose of IV morphine ranged between 4 milligram (mg) and 26.7 (0.05-0.5 mg/kg) during 70% of the visits. 50% of the patients were admitted after less than 3 hours of ED treatment, 28% of the discharged patients returned to the ED within 3 days (3). Also, as other chronic pain patients, sickle cell disease patients develop opioid induced hyperalgesia (OIH) leading to activation of N- methyl D Aspartate receptors (NMDA) (1).

The use of ketamine, a non-competitive NMDA receptor antagonist, may have the potential to modulate the OIH through impaired sensitization of spinal neurons to nociceptive stimuli and may, therefore, impede development of and blunt neuropathic pain. Extensive search of literature databases showed few published reports and retrospective studies including few patients which have addressed the use of low-dose ketamine in the management of acute painful crises in sickle cell disease (SCD) (4-6). A retrospective study (5) included 5 children and adolescents received a low-dose ketamine infusion for the treatment of sickle cell-related pain demonstrated reduced pain scores in 40% of patients and significant reduction in opioid utilization in only 20% of patients. However, that report was retrospective in nature, non-powered, and included few patients. A recent Canadian retrospective study including 9 adult and adolescent patients demonstrated statistically significant reduced cumulative morphine consumption (146±16.5 mg/day vs. 112.±12.2 mg/day) and pain scores after adding intravenous ketamine in patients with painful sickle cell crises (7). Similarly, another American investigators reported decreased opioid consumption with infusing low-dose ketamine as an adjuvant analgesic in 30 patients presented with sickle cell disease with vaso-occlusive crisis (VOC), that study was retrospective (2). Moreover, in year 2017, a prospective, randomized, double dummy trial was done comparing the adverse effects and analgesic efficacy of low-dose ketamine for acute pain in the ED either by single intravenous push or short infusion. This study shows that low-dose ketamine administered as short infusion is related with a significantly lower rates of feeling of unreality and sedation with no difference in analgesic efficacy in comparison to intravenous push (8)

To the best of investigator's knowledge, there is no large, prospective, comparative, controlled clinical trial investigated in the addition of low-dose ketamine in shortening the ER stays and improving the quality of analgesia in patients with VOC.

Sample Size

A data obtained from a pilot study included 10 patients who received either morphine or ketamine showed that the mean and SD of pain visual analogue score (VAS) at 1-hour following administering the study drug among patients presented with sickle-cell VOC were (Morphine 6.5 ± 3.41565, Ketamine: 1.6667 ± 1.52753).

An a priori power analysis indicated that a sample size of 220 patients is sufficiently large to detect a mean difference in the pain VAS of 1.5 that would have a clinical importance, with a type-I error of 0.05 and a power of 90%. Additional patients (20%) will be added for a final sample size of 264 patients to compensate for those dropping out during the study.

Interim Analysis

An independent safety committee will perform three interim analyses on information time 25% (55 patients), 50% (110 patients) and 75% (165 patients). Data evaluation at each interim analysis will be based on the alpha spending function concept, according to Lan and DeMets, and will employ O'Brien-Fleming Z-test boundaries, which are very conservative early in the trial. For the first interim analysis the efficacy stopping rule would require an extremely low P value (P\< 0.000015). For the second interim analysis P\< 0.003 will be taken as efficacy stopping rule. For the third interim analysis P\< 0.02 will be taken as efficacy stopping rule. Investigators will be kept blind to the interim analysis results.

Arms: arm 1: Patients will receive standard dose of morphine (0.1 mg/kg) in 100 ml normal saline (NS) infused over 30 minutes in addition to standard IV hydration. arm 2: Patients will receive low dose ketamine 0.3 mg/kg in 100ml normal saline (NS) infused over 30 minutes in addition to standard IV hydration
Interventions: intervention 1: Morphine Group intervention 2: Ketamine Group intervention 3: standard IV hydration
Intervention descriptions: intervention 1: Patients will receive standard dose of morphine (0.1 mg/kg) in 100 ml normal saline infused over 30 min in addition to standard IV hydration. intervention 2: Patients will receive low dose ketamine 0.3 mg/kg in 100ml N.S. infused over 30 min in addition to standard IV hydration intervention 3: IV hydration as per our institutional protocol (Lactated Ringer's or NaCl 0.9% solution will be infused at a rate of 2-3 ml/kg/h)

Protocol documents:
Prot_SAP_000.pdf: 
Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
 
Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective 
Randomized Control trial 
 
NCT 03431285 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
Brief Summary: 
 
Investigators hypothesize that administration of ketamine for pain relief in sickle cell patients 
with vaso-occlusive crisis early on will lead to a more rapid improvement in pain score and 
less narcotic requirement. 
 
Detailed Description: 
Sickle cell disease is an inherited hematological disorder where the shape of red blood cells is 
altered into a sickle-like cells resulting in red blood cell destruction and therefore anemia and 
other complications. It’s a widely spread condition in African American population as well as 
the Southern and Eastern Provinces of Arabian Peninsula. 
 
Acute painful episodes are a very common complication of the disease process, mainly 
thought to be a result of tissue ischemia due to occlusion of the microcirculation with clusters 
of sickled RBC(1). This usually involves long bones or spine but can involve other areas. 
Acute painful crises can also be precipitated by cold exposure, dehydration, infection, 
hypoxia, acidosis or hypercarbia, or in some cases it is not related to a specific trigger. This 
condition puts the patient in severe pain requiring multiple Emergency Department (ED) 
visits and sometimes admission to the hospital. Currently the mainstay of therapy for acute 
painful crises is hydration and IV opioid analgesia (2). This makes pain control challenging 
for the emergency physician as management of acute painful crises requires multiple doses of 
IV opioids, a retrospective study of 19 patients and 57 visits showed that accumulative dose 
of IV morphine ranged between 4 mg and 26.7 (0.05-0.5 mg/kg) during 70% of the visits. 
50% of the patients were admitted after less than 3 hours of ED treatment, 28% of the 
discharged patients returned to the ED within 3 days (3). Moreover, as other chronic pain 
patients, sickle cell disease patients develop opioid induced hyperalgesia (OIH) leading to 
activation of N- methyl D Aspartate receptors (NMDA) (1). 
 
The use of ketamine, a non-competitive NMDA receptor antagonist, may have the potential 
to modulate the OIH through impaired sensitization of spinal neurons to nociceptive stimuli 
and may, therefore, impede development of and blunt neuropathic pain. Extensive search of 
the literature database showed few published reports and retrospective studies including few 
patients which have addressed the use of low-dose ketamine in the management of acute 
painful crises in SCD (4-6). A retrospective study (5) included 5 children and adolescents 
received a low-dose ketamine infusion for the treatment of sickle cell-related pain 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
demonstrated reduced pain scores in 40% of patients and significant reduction in opioid 
utilization in only 20% of patients. However, that report was retrospective, non-powered, and 
included few patients. A recent Canadian retrospective study including 9 adult and adolescent 
patients demonstrated statistically significant reduced cumulative morphine consumption 
(146±16.5 mg/day vs. 112.±12.2 mg/day) and pain scores after adding intravenous ketamine 
in patients with painful sickle cell crises (7). Similarly, another American investigators 
reported decreased opioid consumption with infusing low-dose ketamine as an adjuvant 
analgesic in 30 patients presented with sickle cell disease with VOC, that study was 
retrospective (2). Moreover, in year 2017, a prospective, randomized, double dummy trial 
was done comparing the adverse effects and analgesic efficacy of low-dose ketamine for 
acute pain in the ED either by single intravenous push or short infusion. This study shows 
that low-dose ketamine administered as short infusion is related with a significantly lower 
rates of feeling of unreality and sedation with no difference in analgesic efficacy in 
comparison to intravenous push (8)  
To the best of our knowledge, there is no a large, prospective, comparative, controlled 
clinical trial investigated the addition of low-dose ketamine in shortening the ER stays and 
improving the quality of analgesia in patients with VOC. 
 
MAIN RESEARCH QUESTION  
Does adding ketamine to the standard acute opiate treatment for pain relief in sickle cell 
patients with vaso-occlusive crisis at an earlier stage lead to a more rapid improvement in 
pain score, less narcotics requirement, and help shorten ER stay for pain management? 
 
Hypothesis 
We hypothesize that administration of ketamine for pain relief in sickle cell patients with 
vaso-occlusive crisis early on will lead to a more rapid improvement in pain score and less 
narcotic requirement. 
 
 
TRIAL DESIGN  
This project is a small scale university hospital prospective, double-blind, RCT of 264 
patients that requires opiate treatment to evaluate the effectiveness of Ketamine in managing 
pain. 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
 Control Group: Patients will receive standard dose of morphine (0.1mg/kg in 0.9% 
Sodium Chloride 100ml bag) in addition to standard IV hydration. 
 Intervention Group: Patients will receive low dose ketamine (0.3 mg/kg in 0.9% 
Sodium Chloride 100ml bag) in addition to standard IV hydration.  Plus morphine 
0.1mg/kg rescue doses.  
 Primary Purpose: Treatment 
 
Sample Size 
A data obtained from a pilot study included 10 patients who received either morphine or 
ketamine showed that the mean and SD of pain visual analogue score (VAS) at 1-hour 
following administering the study drug among patients presented with sickle-cell VOC 
were (Morphine 6.5 ± 3.41565, Ketamine: 1.6667 ± 1.52753). An a priori power analysis 
indicated that a sample size of 220 patients is sufficiently large to detect a mean 
difference in the pain VAS of 1.5 that would have a clinical importance, with a type-I 
error of 0.05 and a power of 90%. Additional patients (20%) will be added for a final 
sample size of 264 patients to compensate for those dropping out during the study.  
 
Interim Analysis  
An independent safety committee will perform three interim analyses on information time 
25% (55 patients), 50% (110 patients) and 75% (165 patients). Data evaluation at each 
interim analysis will be based on the alpha spending function concept, according to Lan 
and DeMets, and will employ O’Brien-Fleming Z-test boundaries, which are very 
conservative early in the trial. For the first interim analysis the efficacy stopping rule 
would require an extremely low P value (P< 0.000015). For the second interim analysis 
P< 0.003 will be taken as efficacy stopping rule. For the third interim analysis P< 0.02 
will be taken as efficacy stopping rule. Investigators will be kept blind to the interim 
analysis results. 
 
INCLUSION CRITERIA  
We will include patients who signed an informed consent that meets the criteria 
below: 
1) Known diagnosis of SCD based on sickle cell tests and hemoglobin 
electrophoresis. 
2) Age 18 to 60 years 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
3) Both genders 
4) Acute onset of painful crises, defined as having an onset within 7 days 
 
EXCLUSION CRITERIA 
1) Pregnancy or breast-feeding 
2) Altered mental status 
3) Body mass index greater than 40 kg/m2 
4) Patients with significant neurological disease 
5) Seizures 
6) Acute head or eye injury 
7) Patients with high intra-cranial tension 
8) Patients with known psychiatric disorders 
9) Patients with significant cardiac diseases or arrhythmias 
10) Patients with significant pulmonary diseases rather than acute chest syndrome 
11) Patients with significant renal disease (BUN/creatinine ratio < 25) 
12) Patients with significant hepatic disease (Child Pugh class B or C) 
13) Patients with significant endocrine disease 
14) Known allergy to phencyclidine derivatives, ketamine or morphine 
15) Sepsis or septic shock 
16) Patients required circulatory or ventilatory supports 
17) Alcohol or drug abuse 
18) Patients with chronic pain status unrelated to SCD 
19) Patients receiving anti-convulsant or anti-psychiatric medications, narcotics, 
analgesics other than paracetamol and NSAID 
20) Patients with communication barriers. 
 
RECRUITMENT AND INFORMED CONSENT 
All physicians and nurses at the Emergency Department will be invited to an in-service trial 
lecture. Pharmacy staff shall likewise be invited to attend this lecture to be conducted by the 
Principal investigator to encourage screening of patients during their shift. Adult patients 
with sickle cell disease who will be admitted to the emergency department solely for pain 
management for severe painful crisis (Numerical Pain rating score (NPRS) greater than 5 on 
a standard 0: no pain to 10: worst imagined pain (appendix 2) who require opioid analgesia, 
as will be determined by the attending physician.  


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
Immediately upon identification of patients with chief complaints or visit reasons of sickle 
cell, study investigators shall screen potentially eligible patients with inclusion/exclusion 
criteria checklist as per Data Collection instrument. If patient is eligible, study investigators 
would obtain informed consent and explain potential risks and benefits with receiving study 
interventions. 
 
RANDOMIZATION  
Randomization will be made after a patient is considered eligible and a written informed 
consent is obtained. Study pharmacist will randomize patients via an electronic pre-generated 
randomization system. The randomization process will use block randomization stratified by 
the system thru the previous use of narcotic drug >24 hours prior to randomization and 
gender. We will use randomly varying block sizes, and will randomize patients in a 1:1 trend 
to receive low dose ketamine 0.3 mg/kg in 100ml normal saline in addition to standard IV 
hydration plus morphine 0.1mg/kg rescue doses vs standard dose of morphine (0.1mg/kg) in 
100 ml normal saline in addition to standard IV hydration plus rescue morphine doses. 
 
MINIMIZING BIAS  
The procedure for randomization warrants confidentiality. All enrolled patients will receive 
the same designed follow-up. We will use the intention-to-treat principle for all analyses.  
 
TRIAL INTERVENTION 
 
Upon arrival and assessment, all patients shall receive a standard dose of non-narcotic 
analgesia, either Paracetamol or NSAID. Pain score will then be measured at 0 and 30 
minutes; after which, consent procedure and randomization shall be initiated provided that 
patients rate their pain (NPRS) greater than 5 and the diagnosis of the painful crises had been 
established.   
 
All health care providers are blinded to the arm. The infusion preparation will be labeled for 
the patient, with study number from the pharmacy, but without any other identifying marks.  
The nurse assigned to the patient would administer the intervention.  
 
Patients randomized to intervention group will receive low dose ketamine 0.3 mg/kg in 
100ml normal saline infused over 30 min in addition to standard IV hydration plus morphine 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
0.1mg/kg rescue doses based on treating physician discretion while patients randomized to 
control group will receive standard dose of morphine (0.1mg/kg) in 100 ml normal saline 
infused over 30 minutes in addition to standard IV hydration plus rescue morphine doses 
based on treating physician discretion. 
 
Pain score will be checked at 0, 30, 60, 90 and 120 minutes. 
If patients rate their pain as lower than 4 at least 2 hours after the administration of either 
medication, patients can be discharged.  
If no pain relief was achieved after 1 dose of therapy, it will be up to the treating physician to 
resume usual practice of managing painful crises with morphine equivalent or admission.  
Patient monitoring includes electrocardiography, non-invasive blood pressure, pulse oximetry 
and temperature. All patients will receive oxygen supplementation through a face mask or 
nasal prongs during sleep and when required to maintain oxygen saturation higher than 90%. 
Lactated Ringer’s or NaCl 0.9 solution will be infused at a rate of 2-3 ml/kg/h. 
Normothermia will be maintained with warming air enforced blankets. 
Patient’s admission to the hospital or home discharge will be left to the discretion of the 
treating physician.  No attempt will be made to expedite this process; the patient will only be 
discharged from the ER if he/she is alert, oriented to the time and place, conversant, and 
cooperative, and if vital signs have been stable for at least 2 hours, the patient can sit up 
without dizziness or nausea, the pain is considered tolerable with an orally administered 
analgesic and no more parenteral analgesia is required.  
 
TRIAL OUTCOMES  
PRIMARY OUTCOME  
 Severity of pain scores using NPRS: the patient will be asked to rate 
his/her pain at the initial assessment, and then the score will be recorded 
by the ED nurse every thirty minutes until discharge from the ED, as part 
of the follow-up. 
 Length of stay in the ED, defined as the time elapsed from the start of 
study medication to the readiness for the discharge from the hospital. 
 Development of any known Side effect of the drugs used. 
 
SECONDARY OUTCOMES  
 The cumulative use of opioid will be recorded during the ED stay 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
 The rate of hospital admission 
 The overall patients’ satisfaction using NPRS (0: no pain, 10: the most 
unimaginable pain). 
 
ADVERSE EVENT REPORTING  
We will describe serious adverse events (SAEs) as any manifestation, incident, or response to 
intervention, whether anticipated or not that needs an in-patient admission or extension of an 
existing hospitalization that results in disability, life threatening occurrence and death.  
 
DATA ANALYSES    
We will analyze patients in the management group to which they are allocated, according to 
the intention-to-treat principle. We will include all randomized patients in these analyses. We 
will compare patients allocated to Ketamine and allocated to standard care. The data will be 
analyzed using SPSS 15.0 software (SPSS, Inc., Chicago, IL, USA) and tested for normal 
distribution using the Kolmogorov–Smirnov test. Continuous variables will be expressed as 
the mean ± SD or as the median and range or 95% confidence intervals (95% CI) if the 
assumption of a normal distribution is violated. Categorical variables will be expressed as 
numbers and percentages. The independent-t-test, Mann–Whitney U test and the Wilcoxon 
rank-sum test, and the χ2 test or Fisher’s exact test will be used as needed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
REFERENCES 
1. Neri, C.M., Pestieau, S.R., Young, H., Elmi, A., Finkel, J.C., et al. (2014) Low-dose 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
Ketamine for Children and Adolescents with Acute Sickle Cell Disease Related Pain: 
A Single Center Experience. Journal of of Anesthesia and Clinical Research 5:394. 
2. Gowhari M, Chu A, Golembiewski, J. (2013). Low-Dose Ketamine Infusion In Adult 
Patients With Sickle Cell Disease – Impact On Management Of Acute Painful 
Episodes. Blood, 122(21), 2249. Accessed August 27, 2017. Retrieved from 
http://www.bloodjournal.org/content/122/21/2249 
3. Solomon L. Pain management in adults with sickle cell disease in a medical center 
emergency department. Journal Of The National Medical Association [serial online]. 
November 2010;102(11):1025-1032. Available from: CINAHL Plus with Full Text, 
Ipswich,MA. Accessed June 21, 2015. 
4. Meals CG, Mullican BD, Shaffer CM, Dangerfield PF, Ramirez RP. Ketamine 
infusion for sickle cell crisis pain in an adult. J Pain Symptom Manage. 
2011;42(3):e7-9. 
5. Okon T. Ketamine: an introduction for the pain and palliative medicine physician. 
Pain Physician 2007;10: 493-500 
6. Zempsky WT, Loiselle KA, Corsi JM, Hagstrom JN. Use of low-dose ketamine 
infusion for pediatric patients with sickle cell disease-related pain: a case series. Clin J 
Pain. 2010;26(2): 163-7. 
7. Tawfic QA, Faris AS, Kausalya R. The role of low dose ketamine midazolam regimen 
in the management of severe painful crisis in patients with sickle cell disease. 2014 
Feb;47(2):334-40. doi: 10.1016/j.jpainsymman.2013.03.012. Epub 2013 Jul 12. 
https://www.ncbi.nlm.nih.gov/pubmed/23856095 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
8. Motov S, Mai M, Pushkar I, Likourezos A, Drapkin J, Yasavolian M, Brady J, Homel 
P, Fromm C. A prospective randomized, double-dummy trial comparing IV push low 
dose ketamine to short infusion of low dose ketamine for treatment of pain in the ED. 
Am J Emerg Med. 2017 Aug;35(8):1095-1100. doi: 10.1016/j.ajem.2017.03.004. 
Epub 2017 Mar 3. 
 
9. New York State Department of Health: Ketamine drug formulary; 
https://www.health.ny.gov/professionals/ems/pdf/ketamine_formulary 
10. De Kock M, Lavand'homme P, Waterloos H. Balanced analgesia' in the perioperative 
period: is there a place for ketamine? 
https://www.ncbi.nlm.nih.gov/pubmed/11376910. 2001 Jun;92(3):373-80. 
11. Fine, PG. Low-dose ketamine in the management of opioid nonresponsive terminal 
cancer pain. http://dx.doi.org/10.1016/S0885-3924(98)00144-4 
12. Beaudoin FL, Lin C, Guan W, Merchant RC. Low dose ketamine improves pain relief 
in patients receiving intravenous opioids for acute pain in the emergency department: 
results of a randomized double blind clinical trial. Acad Emerg Med. 2014 
Nov;21(11):1193-202. doi: 10.1111/acem.12510. 
https://www.ncbi.nlm.nih.gov/pubmed/25377395 
 
15. APPENDICES: 
15.1   Appendix 1: Outcome definitions 
15.3 
Appendix 2: Numerical Pain rating score 
  
Appendix 1: 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 2: 
 
 


Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients:  Prospective Randomized Control trial 
NCT 03431285 04-Feb-2018 
a. NPRS=NUMERICAL PAIN RATING SCORE 
 
 
 
 
 
 
 
b. RICHMOND AGITATION SEDATION SCORE (RASS) 
 
+4  
Combative: Combative, violent, immediate danger to staff 
+3  
Very Agitated: pulls or removes tubes or catheters; aggressive 
+2  
Agitated: frequent non-purposeful movement 
+1  
Restless: anxious and apprehensive, but movements not 
aggressive or vigorous 
 0  
Alert and Calm 
-1  
 Drowsy: appears sleepy, easily alerts, holds attention for >10s 
-2   
Light sedation: sleeping, but awakens to voice or physical 
stimulation  
-3   
Moderate sedation: movement or eye opening to voice, no eye 
contact 
-4   
Deep sedation: arouses to physical stimulation 
-5   
Unarousable 
 
 
 

ICF_001.pdf: 
 
 
 
 
 
Version 1- December 01, 2017
 
 
وزارة التعلي
ــــــــ
م العـــــــــالي 
MINISTRY OF EDUCATION
 
ج
ــــــــــــ
امعة الدم
ــــــــــ
ام 
IMAM ABDULRAHMAN BIN 
FAISAL UNIVERSITY
 وكـالة الجـامعة للدراسـات
 العليــــا
والبـــــحث العـــــلمي 
VICE PRESIDENT FOR GRADUATE
 
 STUDIES & SCIENTIFIC RESEARCH
اللجنة الدائمة ألخالقيات 
 البحث على
المخلوقات الحية 
Standing Committee for 
Research Ethics on Living 
Creatures
Ethics 
 
 
 
INFORMED CONSENT STATEMENT
 
 
For children/minors participating in this study, the term 
 “You” addresses both the participant and the parents or legally authorized representative to consent. 
 
 
 
PROJECT TITLE :
Prospective Randomized Control trial
 
Sickle Cell Disease Patients:
 
Ketamine for Acute Painful Crisis in 
Name of the Principal Investigator:
Dr. Mohammed Alshahrani
 
1. You are being asked to participate in our study
the 
 
for
 
trial
Prospective Randomized Control 
 
Cell Disease Patients:
 
in Sickle
Ketamine for Acute Painful Crisis 
 
period/duration of 24 months. You were particularly selected to participate in this study because this is a 
study that tests the benefit of using a medication that controls the pain that Sickle Cell Disease patients 
suffer during painful episodes. This usually involves long bones or spine but can involve other areas. 
Acute painful crises can also be triggered by cold exposure, dehydration (loss of body fluids, mostly 
water that exceeds the amount that is taken in), infection, hypoxia (your body does not have enough 
oxygen), acidosis (when your body fluids contain too much acid), or in some cases it is not related to a 
specific trigger. This condition puts the patient in severe pain requiring multiple ER visits and sometimes 
admission to the hospital. Therefore many such patients receive a drug that suppresses pain
 .
However, there is no evidence base treatment strategy that has proven effective in treating acute pain 
crisis in SCD. In addition, recent research suggests that despite the use of opioids and non-opioid drugs, 
many SCD patients report inadequate pain control with high re-admission rate
 .
In this study, we will enroll patients in the ED to ensure that patients or substitute decision makers are 
interested in participating, and to ensure that the study drugs are given as prescribed. This research 
project is important because the results of the study will have a big impact on the care of patients who 
visit the ER for SCD pain management in the future. 
For research purpose, the procedures to be followed are: If you agree to participate and sign an informed 
consent, the research team will follow you while you are in the Emergency Room. You will receive either 
a low dose Ketamine or the standard opioid therapy. The study product that you will receive shall be 
determined by chance. That is, there is a 50% chance of receiving the Ketamine and a 50% chance of 
receiving the standard opioid treatment. 
 
Patients allocated to receive the low dose Ketamine will receive 0.3mg/kg of Ketamine intravenously and 
will be repeated after 20-30 minutes. The first dose will be administered as soon as possible in addition 
to standard intra venous hydration. 
 
Patients allocated to receive the standard opioid therapy will receive 1 mg of hydromorphone or 
equivalent dose of morphine and will be repeated after 20-30 minutes. The first dose will be administered 
as soon as possible in addition to standard intra venous hydration. 
 
Your pain severity will be checked every 30 minutes until after 2 hours from the initial time the medication 
was given. If no pain relief was achieved after 2 doses of therapy, it will be up to your doctor to resume 
usual practice of managing painful crisis with morphine or you will be admitted to the hospital.  All 
patients in this study will receive the usual nursing and medical care given by the ER team.  
Your participation in the research study is voluntary. Before agreeing to be a part of this study please, 
read and/or listen to the following information carefully.  
Feel free to ask questions if you have any ambiguities. 
 
 


 
 
 
 
 
 
Version 1, December 01, 2017
 
 
 
 
 
وزارة التعلي
ــــــــ
م العـــــــــالي 
MINISTRY OF EDUCATION
 
ج
ــــــــــــ
امعة الدم
ــــــــــ
ام 
IMAM ABDULRAHMAN 
BIN FAISAL UNIVERSITY
 
 وكـالة الجـامعة للدراسـات
العليــــا والبـــــحث العـــــلمي 
VICE PRESIDENT FOR GRADUATE
 
 STUDIES & SCIENTIFIC RESEARCH
 
 اللجنة الدائمة
ألخالقيات 
 البحث على
المخلوقات الحية 
Standing Committee for 
Research Ethics on Living 
Creatures
Ethics 
 
 
 In addition, the investigator will acquire clinical data from your medical record at the hospital.
 
 
Any and all information obtained from your medical records during the study will be confidential. 
Your privacy will be protected at all times. You will not be identified individually in any way as a 
result of your participation in this research. The data collected however, may be used as part of 
publications and papers related to “ Ketamine for Acute Painful Crisis in  Sickle Cell Disease 
Patients: Prospective Randomized Control trial”        
 
 “In case of any unexpected injury or illness during this study, the compensation or the 
necessary medical treatment will be given as per the rules and regulations of the hospital” 
 
Your participation in this study is entirely voluntary. You have rights to discontinue or refuse to 
participate even after initiation of study at any time for any reason. Such refusal will not have any 
negative consequences for you. 
 
Please feel free to talk to the researcher and ask questions. You may also want to talk to your family, 
friends, or your personal doctor or other health care provider about joining this study.  If you decide 
that you would like to participate in the study, you will be asked to sign this form and you will be 
given a copy of the signed form to keep. 
 
After your participation, in case you have any questions and/or concerns about  research, want 
clarification or report any matter related to your participation in the research you may contact  
Dr. Mohammed Alshahrani any time on the number 0556966663 or via email 
msshahrani@iau.edu.sa 
 
In addition, if any new information is learnt, at any time during the research, which might affect your 
participation in the study, you shall be informed. 
 
Principal Investigator of the study will also sign the copy of Informed consent and the signed copy 
of the Informed Consent will be handed over to the Study Participant. Also, Signed copy of 
informed consent has to be kept in the PI file, SCRELC file, and patient’s medical record file. 
 
 
 
I have read or listened to the above information and I have decided that I will participate in the project as 
described above. The researcher has explained me about the study, other beneficial treatments or procedures 
available and also clarified my doubts. I also understand what will be expected of me. If I do not participate, there 
will be no penalty or loss of rights. I can stop participating at any time, even after I have started.  
 
I agree to participate in the study and for my samples to be kept and used for future research on pain 
management in SCD. 
 
 
My signature below also indicates that I have received a copy of this English consent form.  
 
Participant’s signature ………………………………………..          
       
Principal Investigator signature …………………………….. 
 
Witness - I ……………………………………………………..  
                 
 Witness –II …………………………………………………...