Lubiprostone vs Senna in postoperative orthopedic surgery patients with opioid-induced constipation: A double-blind, active-comparator trial

Table 1 Participant characteristics

Characteristics	Intent to treat			Completers
	Lubiprostone	Senna	P value	Lubiprostone	Senna	P value
	n = 28	n = 28		n = 21	n = 22
Age, yr	70.6 ± 12.1	72.5 ± 10.8	0.54	68.9 ± 12.6	69.6 ± 9.6	0.85
Weight, kg	88.5 ± 23.4	84.0 ± 16.7	0.42	93.4 ± 21.7	85.4 ± 17.0	0.20
Days postoperative, d	5.81 ± 2.72	7.71 ± 6.95	0.19	6.10 ± 2.90	6.50 ± 4.21	0.72
Sex, female	20 (74)	15 (54)	0.16	15 (71)	13 (59)	0.53
Race/ethnicity African American Hispanic Unknown White	5 (18) 1 (4) 2 (7) 20 (71)	7 (25) 0 (0) 3 (11) 18 (64)	0.76	6 (27) 0 (0) 0 (0) 16 (73)	4 (19) 1 (5) 1 (5) 15 (71)	0.72
Primary surgery Diagnosis Total knee or hip replacement Spinal surgery Hip/femur fracture Other	14 (50) 8 (14) 5 (9) 1 (2)	21 (75) 5 (18) 1 (4) 1 (4)	0.18	13 (62) 5 (24) 2 (10) 1 (5)	11 (50) 8 (32) 3 (18) 0 (0)	0.64

Data are expressed as absolute n (%) or mean ± SD.

Table 2 Gastrointestinal outcomes: Patient assessment in constipation

Outcome measure	Intent to treat			Completers
	Lubiprostone	Senna	P value	Lubiprostone	Senna	P value
	n = 28	n = 28		n = 21	n = 22
PAC-SYM
Baseline	0.72 ± 0.56	0.93 ± 0.77	0.10	0.76 ± 0.60	0.95 ± 0.81	0.25
Day 7	0.51 ± 0.41	0.63 ± 0.59	0.06	0.57 ± 0.44	0.59 ± 0.58	0.35
Change	-0.22 ± 0.57	-0.29 ± 0.58	0.89	-0.20 ± 0.60	-0.36 ± 0.61	0.61
PAC-QOL
Baseline	1.50 ± 0.64	1.41 ± 0.73	0.63	1.42 ± 0.55	1.32 ± 0.66	0.63
Day 7	1.66 ± 0.59	1.83 ± 0.79	0.35	1.67 ± 0.56	1.82 ± 0.77	0.35
Change	0.99 ± 0.78	0.42 ± 0.84	0.30	0.25 ± 0.78	0.50 ± 0.80	0.61

Data are expressed as absolute numbers (percentage) or mean ± SD. PAC-SYM: Patient assessment of constipation (PAC)-symptoms; PAC-QOL: PAC-quality of life.

Table 3 Gastrointestinal symptoms

Outcome measure	Intent to treat			Completers
	Lubiprostone	Senna	P value	Lubiprostone	Senna	P value
	n = 28	n = 28		n = 21	n = 22
Nausea Baseline Day 7 Change	0.61 ± 0.79 0.39 ± 0.79 0.21 ± 0.92	0.64 ± 0.99 0.46 ± 0.96 0.18 ± 0.86	0.88 0.76 0.88	0.57 ± 0.81 0.38 ± 0.80 0.19 ± 1.03	0.64 ± 1.05 0.50 ± 1.01 0.14 ± 0.83	0.82 0.67 0.85
Cramping Baseline Day 7 Change	0.25 ± 0.70 0.14 ± 0.36 0.11 ± 0.57	0.54 ± 0.84 0.11 ± 0.31 0.43 ± 0.92	0.17 0.69 0.12	0.29 ± 0.78 0.14 ± 0.36 0.14 ± 0.57	0.63 ± 0.90 0.04 ± 0.21 0.59 ± 0.96	0.18 0.28 0.07
Painful bowel movement evacuation effort (straining) Baseline Day 7 Change	1.40 ± 1.50 0.47 ± 0.70 0.64 ± 0.93	0.87 ± 1.46 0.75 ± 1.37 0.42 ± 1.38	0.98 0.55 0.62	1.53 ± 1.55 0.60 ± 0.74 0.58 ± 0.90	1.18 ± 1.60 0.87 ± 1.51 0.78 ± 1.30	0.58 0.72 0.69
Completeness of bowel movement Baseline Day 7 Change	1.56 ± 1.42 0.67 ± 0.97 0.82 ± 1.17	2.00 ± 1.41 0.55 ± 1.23 1.55 ± 2.11	0.23 1.00 0.33	1.53 ± 1.51 0.86 ± 1.03 0.56 ± 1.01	2.10 ± 1.29 0.46 ± 1.06 2.00 ± 1.41	0.12 0.24 0.03
Abdominal pain Baseline Day 7 Change	0.29 ± 0.71 0.07 ± 0.26 0.21 ± 0.69	0.59 ± 1.01 0.04 ± 0.19 0.56 ± 1.05	0.20 0.56 0.16	0.19 ± 0.68 0.05 ± 0.22 0.14 ± 0.73	0.73 ± 1.08 0.00 ± 0.00 0.73 ± 1.08	0.06 0.34 0.04
Time per lavatory attempt Baseline < 5 min 5-10 min > 10 min NA Day 7 < 5 min 5-10 min > 10 min NA	2 (7) 12 (43) 8 (29) 6 (21) 8 (30) 8 (30) 4 (15) 7 (26)	4 (14) 7 (25) 10 (36) 7 (25) 9 (32) 6 (21) 6 (21) 7 (25)	0.40 0.87	0 (5) 11 (52) 7 (33) 3 (14) 7 (32) 3 (14) 5 (23) 7 (32)	3 (14) 5 (23) 8 (36) 6 (27) 7 (33) 7 (33) 4 (19) 3 (14)	0.08 0.66

Data are expressed as absolute numbers (percentage) or mean ± SD. NA: Not significant.

Table 4 Bowel movements and Bristol stool scale

Outcome measure	Intent to treat			Completers
	Lubiprostone	Senna	P value	Lubiprostone	Senna	P value
	n = 28	n = 28		n = 21	n = 22
Number of unsuccessful attempts for bowel movement
Baseline			0.17			0.29
0	10 (36)	11 (39)		5 (24)	7 (32)
1	4 (14)	8 (29)		3 (14)	7 (32)
2-3	10 (36)	5 (18)		9 (43)	4 (18)
4+	4 (14)	4 (14)		4 (19)	4 (18)
Day 7			0.31			0.60
0	15 (75)	17 (61)		10 (48)	14 (64)
1	6 (21)	7 (25)		6 (29)	5 (23)
2-3	7 (25)	4 (14)		5 (24)	3 (14)
4+	0 (0)	0 (0)		0 (0)	0 (0)
Change (improved)	9 (32)	12 (43)	0.42	12 (57)	13 (59)	0.92
Number of bowel movement
Baseline	0.96 ± 1.17	0.61 ± 0.83	0.19	0.95 ± 0.92	0.64 ± 0.90	0.26
Day 7	0.93 ± 0.90	0.93 ± 0.86	1.00	0.95 ± 0.92	0.91 ± 0.87	0.87
Change	-0.04 ± 1.50	0.32 ± 0.90	0.29	0.00 ± 1.22	0.27 ± 0.98	0.42
Consistency of bowel movement (Bristol stool scale)
Baseline			0.18			0.20
Type 1	4 (14)	0 (0)		4 (19)	0 (0)
Type 2	1 (4)	2 (17)		1 (5)	2 (9)
Type 3	3 (11)	4 (14)		2 (5)	3 (14)
Type 4	1 (4)	3 (11)		1 (5)	1 (5)
Type 5	2 (7)	0 (0)		2 (10)	0 (0)
Type 6	4 (14)	2 (7)		2 (10)	2 (9)
Type 7	1 (4)	0 (0)		1 (5)	0 (0)
NA	12 (43)	17 (59)		8 (38)	14 (64)
Day 7			0.32			0.22
Type 1	4 (14)	0 (0)		4 (19)	0 (0)
Type 2	1 (4)	4 (14)		1 (5)	4 (18)
Type 3	2 (7)	2 (7)		1 (5)	1 (5)
Type 4	6 (21)	10 (36)		5 (24)	8 (36)
Type 5	1 (4)	0 (0)		0 (0)	0 (0)
Type 6	2 (7)	2 (7)		2 (10)	1 (5)
Type 7	1 (4)	1 (4)		0 (0)	1 (5)
NA	11 (39)	9 (32)		8 (38)	7 (32)

Data are expressed as absolute numbers (percentage) or mean ± SD. NA: Not significant.

Table 5 Adverse event

System/adverse event	Any adverse event
	Lubiprostone	Senna
	n = 31	n = 29
Number receiving at least one dose
Number of participants with any event	14 (45.2)	12 (41)
Gastrointestinal disorders
Nausea	3 (9.7)	5 (17.2)
Diarrhea	5 (16.1)	2 (6.9)
Abdominal pain	8 (25.8)	2 (6.9)
Abdominal cramping	6 (19.4)	6 (20.7)
Constipation	0	1 (3.4)
Nervous system disorders
Headache	0	1 (3.4)
Skin disorders rash	0	1 (3.4)
Musculoskeletal disorders
Patellar dislocation	1 (3.2)	0
Laboratory evaluations	0
Hematologic	0	1 (3.4)
Cardiovascular disorders
Cardiomyopathy		1 (3.4)
Total events	23	20

All adverse events in participants receiving at least one dose of study medication. Data are expressed as absolute numbers (percentage) or mean ± SD.