Clinical trial NCT03441269
Conditions: Pain, Acute
Keywords: Emergency Medicine Acute Pain Oral Ibuprofen
Sponsor: Antonios Likourezos
Start date: 2018-11-01; Completion date: 2019-08-31
Enrollment: 225 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Ibuprofen is one of the most widely used non-steroidal anti-inflammatory drug (NSAID) for management of mild -to moderate pain in the ED (acute musculo-skeletal pain, headache, dental pain). Ibuprofen as a representative of NSAID's as a class follows the analgesic ceiling concept that postulates that there is a dose of a drug beyond which any further dosage increase results in no additional analgesic effect. Despite this fact, Ibuprofen may commonly be used at doses above its analgesic ceiling, although this may not offer an incremental analgesic advantage and potentially adds risk of harm. The analgesic ceiling dose for ibuprofen is only 200-400mg/dose, and about 1200 mg/day. Thus, we hypothesize that administration of Ibuprofen in a dose of 400 mg in the ED is as effective in treating mild-to-moderate acute pain in patients presenting to the ED as 600 mg and 800 mg

Detailed description:
STUDY DESIGN A randomized, double-blind trial to determine the analgesic equivalency of orally administered ibuprofen at 400 mg for the treatment of acute pain in comparison to with higher doses of 600 and 800 mg for managing mild-to-moderate pain of adult patients in the ED.

OUTCOME MEASURES The primary outcome will be reduction in numeric rating scale pain score at 60 minutes from medication administration. Secondary outcomes included rates and percentages of subjects experiencing adverse effects as well as percentage of patients requiring rescue analgesia

STUDY POPULATION Patients considered for inclusion will comprise adults aged 18 and older years who presented to the ED primarily for management of acute mild to moderate musculoskeletal pain, headache, or dental pain who would routinely be treated with oral iburpofen in our ED as determined by the treating attending or resident physician. Acute pain will be defined in our study as having an onset within 30 days or less. Exclusion criteria will include pregnancy or breastfeeding, active peptic ulcer disease, acute gastrointestinal hemorrhage, known history of severe renal or hepatic insufficiency, allergy to nonsteroidal anti-inflammatory drugs, and patients having already received analgesic medication. For the purposes of this study, ibuprofen will be used without co-administration of any other analgesics, with the exception of rescue medication.

STUDY LOCATION The study will be conducted at a 711-bed urban community teaching hospital with an annual ED census of greater than 120,000 visits.

DURATION OF ENROLLMENT Patients pain scores will be recorded at the beginning of the study and at 60 minutes post-administration of medication by utilizing NRS.

DESCRIPTION OF INTERVENTION AND ADMINISTRATION Once the patient is triaged, an initial pain score will be assessed. Patients will then have an initial evaluation by ED physician and, once deemed eligible for the study, the patient will be randomized to receive oral ibuprofen at a dose of 400mg, 600mg, or 800mg. The on-duty ED pharmacist will prepare 400 mg, 600 mg and 800 mg oral ibuprofen preparations in identical capsules according to predetermined randomization generated in SPSS by the research manager. Demographics, chief complaint and initial pain score will be recorded in the data sheet as well as prior analgesics use. Patients pain scores will be recorded at the beginning of the study and at 60 minutes post-administration by using NRS.

RANDOMIZATION/BLINDING The research manager and statistician independently of data collection will conduct the programming of the randomization list, confirmation of written consent acquisition, and statistical analyses. ED pharmacy investigators will maintain the randomization list, prepare the medication, and deliver it to the nurse caring for the study participant in a blinded manner. The preparing pharmacist, research manager, and statistician will be the only ones with knowledge of the study arm to which the participant would be randomized. Providers, participants, and the data-collecting research team will be blinded to the medication received. Study investigators will include treating physicians who will assisted in screening and supervising the research fellow, residents, and research coordinators, who will enroll patients and record pain scores and adverse effects at baseline and at 60 minutes.

Arms: arm 1: Oral Ibuprofen dose of 400mg/dose for mild to moderate acute pain in ED patients. arm 2: Oral Ibuprofen dose of 600mg/dose for mild to moderate acute pain in ED patients. arm 3: Oral Ibuprofen dose of 800mg/dose for mild to moderate acute pain in ED patients.
Interventions: intervention 1: Oral Ibuprofen
Intervention descriptions: intervention 1: Oral Ibuprofen will be given to all the arms; only the dosage will be different: 400mg vs. 600mg vs. 800mg

Protocol documents:
Prot_SAP_000.pdf: 
Title:  A Prospective Randomized Double-Blind Trial Comparing 3 Doses of Oral Ibuprofen in 
Management of Mild to Moderate Pain of Adult Patients in the ED 
 
Date: May 1, 2018 
 
NCT#: NCT03441269 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
INTRODUCTION: 
Ibuprofen is one of the most widely used non-steroidal anti-inflammatory drug (NSAID) for 
management of mild -to moderate pain in the ED (acute musculo-skeletal pain, headache, dental 
pain). Ibuprofen as a representative of NSAID's as a class follows the analgesic ceiling concept 
that postulates that there is a dose of a drug beyond which any further dosage increase results in 
no additional analgesic effect. Despite this fact, Ibuprofen is commonly used in the ED at doses 
above its analgesic ceiling (600-800 mg per dose), although this may not offer an incremental 
analgesic advantage and potentially adds risk of harm. The proposed analgesic ceiling dose for 
ibuprofen is only 200-400 mg/dose, and about 1200 mg/day. Thus, we propose that 
administration of Ibuprofen in a dose of 400 mg in the ED is as effective in treating mild-to-
moderate acute pain in patients presenting to the ED as 600 mg and 800 mg. To our knowledge, 
there are no data from EM literature that directly evaluated the analgesic ceiling dose of 
Ibuprofen for managing pain in the ED. 
 
STUDY DESIGN 
A randomized, double-blind trial to determine the analgesic equivalency of orally administered 
ibuprofen at 400 mg for the treatment of acute pain in comparison to with higher doses of 600 
and 800 mg for managing mild-to-moderate pain of adult patients in the ED. 
 
OUTCOME MEASURES 
The primary outcome will be reduction in numeric rating scale pain score at 60 minutes from 
medication administration. Secondary outcomes included rates and percentages of subjects 
experiencing adverse effects as well as percentage of patients requiring rescue analgesia 
 
STUDY POPULATION 
Patients considered for inclusion will comprise adults aged 18 and older years who presented to 
the ED primarily for management of acute mild to moderate musculoskeletal pain, headache, or 
dental pain with an intensity of less than 4 on a standard 0 to 10 numeric rating scale and who 
would routinely be treated with oral iburpofen in our ED as determined by the treating attending 
or resident physician. Acute pain will be defined in our study as having an onset within 30 days 
or less. Exclusion criteria will include pregnancy or breastfeeding, active peptic ulcer disease, 
acute gastrointestinal hemorrhage, known history of severe renal or hepatic insufficiency, allergy 
to nonsteroidal anti-inflammatory drugs, and patients having already received analgesic 
medication. For the purposes of this study, ibuprofen will be used without co-administration of 
any other analgesics, with the exception of rescue medication. 
 
STUDY LOCATION 
The study will be conducted at a 711-bed urban community teaching hospital with an annual ED 
census of greater than 120,000 visits. 
 
DURATION OF ENROLLMENT 


Patients pain scores will be recorded at the beginning of the study and at 60 minutes post-
administration of medication by utilizing NRS. 
 
 
 
DESCRIPTION OF INTERVENTION AND ADMINISTRATION 
Once the patient is triaged, an initial pain score will be assessed. Patients will then have an initial 
evaluation by ED physician and, once deemed eligible for the study, the patient will be 
randomized to receive oral ibuprofen at a dose of 400mg, 600mg, or 800mg. The on-duty ED 
pharmacist will prepare 400 mg, 600 mg and 800 mg oral ibuprofen preparations in identical 
capsules according to predetermined randomization generated in SPSS by the research manager. 
Demographics, chief complaint and initial pain score will be recorded in the data sheet as well as 
prior analgesics use. Patients pain scores will be recorded at the beginning of the study and at 60 
minutes post-administration by using NRS. 
 
RANDOMIZATION/BLINDING 
The research manager and statistician independently of data collection will conduct the 
programming of the randomization list, confirmation of written consent acquisition, and 
statistical analyses. ED pharmacy investigators will maintain the randomization list, prepare the 
medication, and deliver it to the nurse caring for the study participant in a blinded manner. The 
preparing pharmacist, research manager, and statistician will be the only ones with knowledge of 
the study arm to which the participant would be randomized. Providers, participants, and the 
data-collecting research team will be blinded to the medication received. Study investigators will 
include treating physicians who will assisted in screening and supervising the research fellow, 
residents, and research coordinators, who will enroll patients and record pain scores and adverse 
effects at baseline and at 60 minutes. 
 
STATISTICAL ANALYSES 
All data will be recorded on data sheets separate from clinical data and entered into Microsoft 
Excel. The Microsoft Excel spreadsheet will be exported to SPSS 19.0 for statistical analyses. Data 
will be analyzed by intention to treat and will include frequency distributions, and repeated 
measures ANOVA to assess a difference in pain scores. The chi-square test will assess the presence 
or absence of side effects between the three groups. A p-value of < 0.05 will be used to denote 
statistical significance.