Economic Impact of Preoperative Meloxicam IV Administration in Total Knee Arthroplasty: A Randomized Trial Sub-Study

Figures & data

Table 1. Enrolled subjects.

Measures of interest	Meloxicam IV		Placebo		p-value^b
	N	%	N	%
All Enrolled Subjects	93	51.4%	88	48.6%
Age (years)
Mean (SD)	66.9 (8.23)		65.5 (8.11)		0.2730
Age ≥65 years	58	62.4%	54	61.4%	0.8897
Sex					0.9880
Male	39	41.9%	37	42.0%
Female	54	58.1%	51	58.0%
Race					0.9992
White	74	79.6%	70	79.5%
Black/African American	18	19.4%	17	19.3%
Asian	1	1.1%	1	1.1%
Ethnicity					0.9017
Hispanic or Latino	9	9.7%	9	10.2%
Not Hispanic or Latino	84	90.3%	79	89.8%
BMI (kg/m^2 )
Mean (SD)	30.6 (4.74)		31.5 (5.05)		0.1991
Insurance type					0.7294
Private	51	54.8%	46	52.3%
Medicare/Other^a	42	45.2%	42	47.7%
Was the quadriceps tendon spared during surgery?					0.3722
Yes	67	72.0%	58	65.9%
No	26	28.0%	30	34.1%

BMI, Body mass index; SD, Standard deviation.

^a Only 4 patients had "other" health insurance which includes CHAMPVA (n = 1), Medicaid (n = 1), Medicare/United health (n = 1) and Medicare/Medicaid (n = 1).

^b p-values for the comparison between meloxicam IV and placebo groups were obtained using chi-square tests.

Table 2. Total Costs of Hospital Stay.

Measures of interest	Meloxicam IV (N = 93)			Placebo (N = 88)
	mean	SD	median	mean	SD		median	p-value^f
Total costs of hospital stay^a	$29,302	$15,914	$24,451	$31,821	$22,281		$25,273	0.7037
Total costs of hospital stay by^a
Insurance type
Private	$27,072	$11,671	$24,834	$32,152	$21,237		$30,092	0.3608
Medicare/Other^b	$32,011	$19,709	$24,249	$31,459	$23,624		$23,456	0.6007
Whether quadriceps tendon was spared during surgery
Yes	$30,659	$15,220	$30,714	$34,842	$21,225		$31,306	0.3469
No	$25,806	$17,399	$20,337	$25,981	$23,458		$19,892	0.582
AEs of special interest^c
0	$29,633	$16,328	$24,451	$31,516	$21,304		$25,273	0.8236
≥1	$24,501	$6,689	$23,591	$33,756	$28,759		$25,011	0.7431
ORADEs^d
0	$29,612	$17,041	$24,266	$29,916	$17,833		$24,129	0.991
≥1	$28,971	$14,803	$26,175	$32,620	$23,989		$25,980	0.7262
SAEs^e
0	$29,307	$16,074	$24,368	$29,604	$19,188		$24,655	0.9498
≥1	$29,151	$12,331	$35,978	$51,288	$36,526		$34,877	0.5791

AEs, Adverse events; ORADEs, Opioid related adverse drug events; SAEs, Serious adverse events; SD, Standard deviation.

^a A cost to charge ratio (0.477) was applied to convert the charges obtained from UB-04 forms to cost.

Note: Readmission was not captured in the UB-04 form; therefore, charges from UB-04 do not reflect readmission.

^b Only 4 patients have "other" health insurance which includes CHAMPVA (n = 1), Medicaid (n = 1), Medicare/United health (n = 1) and Medicare/Medicaid (n = 1).

^c AEs of special interest refer to the adverse events related to the study drug only (e.g. bleeding, cardiovascular, hepatic, injection site reactions, renal, thrombotic, and wound healing event).

^d ORADEs include adverse events such as gastrointestinal (e.g. nausea, vomiting, constipation, stomach pain, loss of appetite, ileus), central nervous system (e.g. sleepiness, tiredness, drowsiness, dizziness, lightheadedness, weakness, itching, dry mouth) or respiratory effects (e.g. respiratory depression, apnea, respiratory arrest).

^e SAEs include hepatobiliary, renal, cardiovascular, thrombotic, bleeding, wound healing or injection site events.

^f p-values used for comparison between treatment groups were derived using Wilcoxon rank-sum test. P-values for variables with small cell sizes should be interpreted with caution.

Table 3. Hospital Length of Stay (LOS).

Measures of interest	Meloxicam IV (N = 93)			Placebo (N = 88)
	mean	SD	median	mean	SD	median	p-value^e
Hospital LOS in days^a	2.05	0.7	2	2.24	1.18	2	0.3887
Hospital LOS in hours^a	56.35	16.98	55.5	61.19	29.02	55.6	0.4502
Number of days from the date of admission to the date when the hospital discharge order was written	1.97	0.7	2	2.14	1.18	2	0.5933
Hospital LOS (in days) by
AEs of special interest^b
0	2.05	0.71	2	2.25	1.23	2	0.3674
≥1	2.17	0.41	2	2.17	0.83	2	0.9108
ORADEs^c
0	1.96	0.74	2	1.81	0.69	2	0.4526
≥1	2.16	0.64	2	2.42	1.3	2	0.3594
SAEs^d
0	2.03	0.68	2	2.1	0.74	2	0.519
≥1	2.67	1.15	2	3.44	2.83	2	1
Hospital LOS (in hours) by
AEs of special interest
0	56.17	17.37	55.5	61.5	30.23	56.2	0.3944
≥1	58.93	10.52	55.2	59.17	20.67	54	0.6734
ORADEs
0	54.04	17.71	55.4	50.76	16.76	53.7	0.4481
≥1	58.82	16	55.8	65.56	31.94	56.8	0.3995
SAEs
0	55.84	16.66	55.1	57.64	17.85	55.2	0.5781
≥1	71.7	23.5	58.4	92.34	69.53	58	0.7115

AEs, Adverse events; LOS, Length of stay; ORADEs, Opioid-related adverse events; SAEs, serious adverse events; SD, Standard deviation.

^a LOS (in hours and days) was reported as number of hours from hospital admission to discharge (captured in clinical database) as well as the number of days from the date of admission to the date of actual hospital discharge.

^b AEs of special interest refer to the adverse events related to the study drug only (e.g. bleeding, cardiovascular, hepatic, injection site reactions, renal, thrombotic, and wound healing event).

^c ORADEs include adverse events such as gastrointestinal (nausea, vomiting, constipation, stomach pain, loss of appetite, ileus), central nervous system (sleepiness, tiredness, drowsiness, dizziness, lightheadedness, weakness, itching, dry mouth) or respiratory effects (respiratory depression, apnea, respiratory arrest).

^d SAEs include hepatobiliary, renal, cardiovascular, thrombotic, bleeding, wound healing or injection site events.

^e p-values used for comparison between treatment groups were derived using Wilcoxon rank-sum test. P-values for variables with small cell sizes should be interpreted with caution.

Table 4. Clinical endpoint results from Phase IIIB clinical trial by treatment group.

Measures of interest	Meloxicam IV (N = 93)		Placebo (N = 88)		p-value^f
	n/mean (SD)	%/median	n/mean (SD)	%/median
Total use of opioid analgesia from Hour 0 through hospital discharge	33.28 (21.34)	27.7	44.87 (21.76)	44.42	<.0001
Total use of opioid analgesia from hospital discharge through 24-hour telephone interview	5.53 (4.89)	4.6	6.99 (6.12)	5.06	0.1406
AEs of special interest^a
≥1 AEs of special interest	6	6.5%	12	13.6%	0.106
Number of AEs of special interest					0.233
0	87	93.5%	76	86.4%
1	4	4.3%	4	4.5%
2	1	1.1%	5	5.7%
3+	1	1.1%	3	3.4%
ORADEs^b
≥1 ORADES	45	48.4%	62	70.5%	0.003
Number of ORADEs					0.004
0	48	51.6%	26	29.5%
1	23	24.7%	38	43.2%
2	13	14.0%	20	22.7%
3+	9	9.7%	4	4.5%
SAEs^c
≥1 SAEs	3	3.2%	9	10.2%	0.058
Number of SAEs
0	90	96.8%	79	89.8%	0.146
1	3	3.2%	8	9.1%
2+	0	0.0%	1	1.1%
Sum of pain intensity from the time of first dose of study drug through 24 hours	5452.48 (2196.07)	5,299.50	6974.86 (2098.37)	7,184.50	<.0001
Sum of pain intensity from the time of first dose of study drug through 48 hours	10275.11(4321.41)	9,947.50	12720.69 (4267.77)	13,023.00	0.0002
Sum of pain intensity from the time of first dose of study drug through discharge	11989.45 (6901.52)	12,112.00	17141.06(11844.34)	15,220.50	0.0007
PGA score^d (by time)
Hour 0 to 24	2.52 (1.1)	3.0	1.88 (1.07)	2.0	0.0002
Hour 48	2.85 (0.96)	3.0	2.38 (0.84)	2.0	0.0025
Hour 72	2.83 (1.19)	3.0	2.62 (0.74)	3.0	0.5811
OBAS^e score (POD1)	4.38 (2.94)	4.0	5.87 (3.29)	5.0	0.0019
ODDS score (POD1)	1.68 (2.08)	1.0	2.33 (2.54)	2.0	0.0637

AEs, Adverse Events; OBAS, Overall Benefit of Analgesia Score Questionnaire; ODDS, Opioid Dimension Distress Score; ORADEs, Opioid-related adverse events, PGA, Patient Global Assessment; POD, post-operative day; SAEs, Serious adverse events; SD, Standard deviation.

^a AEs of special interest refer to the adverse events related to the study drug only (e.g. bleeding, cardiovascular, hepatic, injection site reactions, renal, thrombotic and wound healing event).

^b ORADEs include adverse events such as gastrointestinal (e.g. nausea, vomiting, constipation, stomach pain, loss of appetite, ileus), central nervous system (e.g. sleepiness, tiredness, drowsiness, dizziness, lightheadedness, weakness, itching, dry mouth) or respiratory effects (e.g. respiratory depression, apnea, respiratory arrest).

^c SAEs include hepatobiliary, renal, cardiovascular, thrombotic, bleeding, wound healing or injection site events.

^d PGA score represents pain control:0-poor, 1-fair, 2-good, 3-very good, or 4-excellent.

^e OBAS score derived from 7 items ranging from 0 = not at all to 4 = very much.

^f As data for sum of pain intensity, PGA scores, OBAS, and ODDS scores was normally distributed, p-values were computed using independent sample t-tests. p-values used for comparison of other continuous variables between treatment groups were derived using Wilcoxon rank-sum test as the data was not normally distributed; p-values for categorical variables were obtained using chi-square tests. P-values were not computed for cell sizes with 0 counts.

Table 5. Multivariable analyses on treatment group and clinical endpoints.

	Total Costs of Hospital Stay				Hospital LOS (days)
	Parameter Estimate	Wald 95% Confidence Limits		p-value	Parameter Estimate	Wald 95% Confidence Limits		p-value
		Lower Limit	Upper Limit			Lower Limit	Upper Limit
Treatment group
Meloxicam IV 30 mg vs Placebo	0.902^c	0.778	1.045	0.1689	0.914	0.819	1.020	0.1082
Clinical endpoints
Opioid consumption (total use of opioid analgesia from Hour 0 through hospital discharge)	0.999	0.996	1.003	0.6480	1.005	1.003	1.008	0.0001
ORADEs^a (≥1 vs 0)	1.039	0.890	1.213	0.6231	1.151	1.024	1.293	0.0183
PGA^b Hour 48	0.996	0.890	1.213	0.9231	0.928	1.024	1.293	0.0024
OBAS score (POD1)	0.984	0.914	1.085	0.2005	1.007	0.884	0.973	0.4924
ODDS (POD1)	0.982	0.960	1.009	0.2940	0.992	0.988	1.026	0.5656

LOS, Length of stay; ORADEs, Opioid-related adverse events; PGA, pain global assessment; OBAS, overall benefit of analgesia; ODDS, opioid distress dimension score.

^a ORADEs include adverse events such as gastrointestinal (nausea, vomiting, constipation, stomach pain, loss of appetite, ileus), central nervous system (sleepiness, tiredness, drowsiness, dizziness, lightheadedness, weakness, itching, dry mouth) or respiratory effects (respiratory depression, apnea, respiratory arrest).

^b PGA score measured from Hour 0 to 48.

^c Note incremental costs of hospital stay were derived using the exponentiated parameter estimate of intercept (exp [10.026] = 23066).

Table 6. Healthcare resource utilization measures from hospital discharge through post-operative day 30.

Parameters of Interest	Meloxicam IV (N = 93)			Placebo (N = 88)
	N/mean (SD)	%	Events	N/mean (SD)	%	Events
All-cause hospital readmissions	1	1.1%	1	3	3.4%	3
ER visits due to pain	0	0.0%	0	4	4.5%	4
Unscheduled doctor visits due to pain	0	0.0%	0	0	0.0%	0
Phone calls due to pain	4	4.3%	4	9	10.2%	9
Subjects requiring skilled nursing facility care after discharge	5	5.4%	N/A	13	14.8%	N/A
Total time spent in skilled nursing facility (days)
Mean (SD)	0.6 (3.12)			1.9 (4.99)
Median (Min, Max)	0 (0, 22)			0 (0,22)

ER, Emergency room; SD, Standard deviation.