IV Tramadol – A New Treatment Option for Management of Post-Operative Pain in the US: An Open-Label, Single-Arm, Safety Trial Including Various Types of Surgery

Figures & data

Table 1 Common Terminology Criteria for Adverse Events Grade

CTCAE Grade	CTCAE Grade Description
Grade 1: Mild	Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
Grade 2: Moderate	Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL.^a
Grade 3: Severe	Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL.^b
Grade 4: Life-threatening	Life-threatening consequences; urgent intervention indicated.
Grade 5: Death	Death related to the AE.

Notes: ^aInstrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. ^bSelf-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 was used for AE grading. A complete CTCAE list can be downloaded at http://evs.nci.nih.gov/ftp1/CTCAE/About.html.

Abbreviations: ADL, Activities of Daily Living; AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events.

Table 2 Demographic and Other Baseline Characteristics

Category	Tramadol 50 mg (N=251) n (%)
Age (years), n	251
Mean (SD)	45.6 (17.26)
Median	48.0
Min, max	(18, 75)
Gender
Male	100 (39.8)
Female	151 (60.2)
Ethnicity
Hispanic or Latino	85 (33.9)
Non-Hispanic/Non-Latino	166 (66.1)
Race
White	203 (80.9)
Black or African American	43 (17.1)
Asian	3 (1.2)
Other	1 (0.4)
Multiple	1 (0.4)
Previous opioid history
Yes	48 (19.1)
No	203 (80.9)
ASA Physical Classification
1	48 (19.1)
2	203 (80.9)
Baseline body mass index (kg/m^2), n	250
Mean (SD)	27.2 (5.09)
Median	26.6
Min, max	(16.5, 39.6)
Surgery Type
Total knee replacement	32 (12.7)
Total hip replacement	57 (22.7)
Abdominoplasty	20 (8.0)
Colon surgeries	15 (6.0)
Hernia surgeries	48 (19.1)
Breast augmentation	77 (30.7)
Hysterectomy	2 (0.8)

Abbreviations: ASA, American Society of Anesthesiologists; max, maximum; min, minimum; SD, standard deviation; n, column number; N, total number.

Table 3 Incidence of Treatment-Emergent Adverse Events Occurring in at Least 2% of Patients

MedDRA Preferred Term	Tramadol 50 mg (N=251) n (%)
Nausea	72 (28.7)
Vomiting	49 (19.5)
Hypoxia	17 (6.8)
Blood creatine phosphokinase increased	16 (6.4)
Constipation	14 (5.6)
Infusion site pain	13 (5.2)
Dizziness	10 (4.0)
Headache	6 (2.4)
Infusion site phlebitis	5 (2.0)

Notes: A TEAE was defined as an adverse event occurring during or after study drug administration and up to 24 h after last study drug administration. For each preferred term, patients experiencing more than one TEAE are only counted once. All TEAEs were coded using the MedDRA, Version 20.1.

Abbreviations: MedDRA, Medical Dictionary for Regulatory Activities; TEAE, treatment-emergent adverse event; n, column number; N, total number.

Table 4 Opioid-Related Adverse Events by Time to Onset Post-First Dose

Preferred Term	Hours Post-First Dose (N=251)
	0–4 Hours n (%)	>4 to 8 Hours n (%)	>8 Hours n (%)
Nausea	49 (19.5)	7 (2.8)	16 (6.4)
Vomiting	35 (13.9)	5 (2.0)	10 (4.0)
Hypoxia	2 (0.8)	4 (1.6)	14 (5.6)
Constipation	0	0	14 (5.6)
Dizziness	5 (2.0)	0	6 (2.4)
Pruritus generalized	1 (0.4)	2 (0.8)	1 (0.4)
Somnolence	3 (1.2)	0	0
Pruritus	2 (0.8)	0	0

Notes: A TEAE is defined as an adverse event occurring during or after study drug administration and up to 24 h after the start of the last study drug administration. Time period category is for the time from first study treatment to first onset of at least one TEAE within each preferred term. All adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA), Version 20.1.

Abbreviations: TEAE, treatment-emergent adverse event; n, column number; N, total number.

Figure 1 Patient global assessment of treatment at 24 and end of study treatment.

Abbreviations: IV, intravenous; PGA, patient global assessment; mg, milligram.