Double-blind, randomized, double-dummy clinical trial comparing the efficacy of ketorolac trometamol and naproxen for acute low back pain

Figures & data

Table 1 Distribution of demographic data at the beginning of the treatment

Demographic data	NA	Ketorolac	P-value
Sex, n (%)
F	19 (46.34)	23 (54.76)	0.51
M	22 (53.66)	19 (45.24)
Age, years, mean (SD)	45.49 (10.98)	45.60 (9.40)	0.962
Weight, kg, mean (SD)	78.95 (13.96)	71.61 (10.89)	0.009a
Clinical changes, n (%)
Y	25 (60.98)	23 (54.76)	0.66
N	16 (39.02)	19 (45.24)
Concomitant medications, n (%)
Y	31 (75.61)	35 (83.33)	0.32
N	8 (19.51)	7 (16.67)
NoA	2 (4.88)	0 (0.00)
Roland–Morris, mean (SD)
ITT	16.02 (5.68)	15.59 (5.37)	0.720
PP	16.35 (5.50)	15.50 (5.60)	0.544
VAS, mean (SD)
ITT	7.68 (1.49)	7.62 (1.43)	0.843
PP	7.77 (1.52)	7.58 (1.41)	0.591

Notes:

a At the beginning of the study, no differences were detected among the groups, except for weight; n, sample.

Abbreviations: F, female; ITT, intention to treat; M, male; N, no; NA, naproxen; NoA, no answer; PP, protocol population; SD, standard deviation; VAS, visual analog scale; Y, yes.

Figure 1 Enrollment and randomization flowchart.

Note: Adverse effect: cholecystitis, improbably associated with the test drug.
Abbreviations: KT, ketorolac trometamol; NA, naproxen.

Table 2 RPR as assessed using VAS scores

Visits	Parameter	µ2 (NA)	µ1 (ketorolac)	µ2–µ1	95% CI (LCL)	95% CI (UCL)	Levene’s testa (P-value)	t-testb (P-value)
V0–60 × V0	RPR	0.258	0.314	−0.056	−0.166	0.055	0.608	0.321
	n	31	33
V1 × V0	RPR	0.387	0.384	0.003	−0.142	0.149	0.882	0.964
	n	31	33
V2 × V0	RPR	0.436	0.479	−0.043	−0.218	0.132	0.323	0.627
	n	30	33

Notes:

a Test for variance equality.

b Test for averages equality. t-test for two independent samples to compare means between two groups.

Abbreviations: CI, confidence interval; NA, naproxen; RPR, rate of pain relief; VAS, visual analog scale; LCL, lower confidence limit; UCL, upper confidence limit.

Table 3 Pain relief as assessed by comparing VAS scores 1 hour before and after receiving medication

Day	Dose	µ2 (NA; n)	µ1 (ketorolac; n)	µ2–µ1	95% CI (LCL)	95% CI (UCL)	Levene’s testa (P-value)	t-testb (P-value)
1	1	0.118 (26)	0.168 (28)	−0.050	−0.162	0.061	0.730	0.370
	2	0.084 (25)	0.127 (28)	−0.042	−0.200	0.115	0.936	0.589
	3	0.084 (22)	0.270 (20)	−0.186	−0.410	0.038	0.003	0/099
2	1	0.166 (25)	0.173 (29)	−0.007	−0.164	0.151	0.771	0.933
	2	0.102 (22)	0.176 (27)	−0.075	−0.233	0.083	0.476	0.339
	3	0.144 (22)	0.240 (24)	−0.096	−0.272	0.079	0.207	0.269
3	1	0.085 (23)	0.179 (27)	−0.094	−0.256	0.067	0.031	0.243
	2	0.06 (24)	0.227 (24)	−0.168	−0.289	−0.055	0.000	0.005
	3	0.112 (22)	0.250 (20)	−0.139	−0.324	0.046	0.360	0.141
	4	−0.042 (3)	0.232 (11)	−0.274	−0.778	0.230	0.461	0.128
4	1	0.108 (16)	0.181 (23)	−0.072	−0.229	0.084	0.299	0.326
	2	0.091 (16)	0.213 (21)	−0.122	−0.274	0.030	0.115	0.089
	3	−0.068 (11)	0.270 (20)	−0.338	−0.560	−0.117	0.528	0.008
	4	0.083 (4)	0.345 (7)	−0.262	−0.673	0.149	0.289	0.118
5	1	0.038 (10)	0.200 (20)	−0.162	−0.395	0.071	0.034	0.165
	2	0.115 (8)	0.275 (19)	−0.160	−0.476	0.155	0.139	0.214
	3	0.056 (6)	0.270 (12)	−0.215	−0.477	0.048	0.035	0.101
	4	0.000 (2)	0.131 (4)	−0.131	−0.524	0.261	0.170	0.258

Notes: n, number of subjects who received the dose.

a Test for variance equality.

b Test for equality of means. t-test for two independent samples to compare means between two groups.

Abbreviations: CI, confidence interval; LCL, lower confidence limit; NA, naproxen; UCL, upper confidence limit; VAS, visual analog scale.

Table 4 Efficacy evaluation for investigator ratings of excellent, very good, or good

Visits	Parameter	Coefficient	SE	P-valuea	OR	95% CI OR
V1	Age	−0.046	0.026	0.076	0.955
	Treatment	1.075	0.5	0.031	2.931	1.10–7.80
	Constant	1.723	1.215	0.156	5.6
V2	Age	−0.051	0.025	0.041	0.950
	Treatment	0.681	0.502	0.210	1.878	0.70–5.03
	Constant	2.360	1.211	0.051	10.594

Note:

a P-value for independent variables coefficient by binary logistic regression.

Abbreviations: CI, confidence interval; OR, odds ratio; SE, standard error.

Figure 2 Pain relief rate 1 hour after medication.

Abbreviation: NA, naproxen.

Table 5 Major adverse effects: incidence as a result of treatment in the ITT population

Effect	Treatment
	NA	Ketorolac
Diarrhea	2	2
Heartburn	6	8
Dry mouth	0	2
Nausea	2	1
Erythematous plaque	1	1
Drowsiness	6	3
Vomiting	3	1

Abbreviations: NA, naproxen; ITT, intention to treat.

Table 6 Percentage of change in laboratory test results for the protocol population on visits 2 (V₂) and 3 (V₃) compared with values obtained on the initial visit (V₀)

Parameter	Visits	P1 (Naprosyn^®)	P2 (Toragesic^®)	P1–P2	95% CI (LCL)	95% CI (UCL)	Levene’s testa (P-value)	t-testb (P-value)
Creatinine	(V0 × V2)	0.086	0.081	0.005	−0.127	0.137	0.889	0.944
	n	35	37
AST	(V0 × V2)	0.029	0.027	0.002	−0.077	0.080	0.938	0.969
	n	35	37
ALT	(V0 × V2)	0.000	0.027	−0.027	−0.082	0.028	0.049	0.334
	n	35	37
Urinalysis
Urine density	(V0 × V2)	0.229	0.405	−0.177	−0.394	0.041	0.002	0.109
	n	35	37
Urine pH	(V0 × V2)	0.171	0.189	−0.018	−0.201	0.165	0.700	0.847
	n	35	37
Urine WBC	(V0 × V2)	0.057	0.027	0.030	−0.065	0.125	0.206	0.529
	n	35	37
Urine RBC	(V0 × V2)	0.143	0.108	0.035	−0.123	0.192	0.380	0.661
	n	35	37
Urine density	(V0 × V3)	0.314	0.270	0.044	−0.173	0.261	0.422	0.686
	n	35	37
Urine pH	(V0 × V3)	0.143	0.189	−0.046	−0.224	0.131	0.298	0.604
	n	35	37
Urine WBC	(V0 × V3)	0.086	0.027	0.059	−0.052	0.169	0.029	0.284
	n	35	37
Urine RBC	(V0 × V3)	0.057	0.054	0.003	−0.106	0.112	0.911	0.955
	n	35	37

Notes:

a Test for variance equality.

b Test for equality of means. t-test for two independent samples to compare means between two groups.

Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; CI, confidence interval; RBC, red blood cells; WBC, white blood cells; P₁, percentage Naprosyn^®; P₂, percentage Toragesic^®; LCL, lower confidence limit; UCL, upper confidence limit.