Randomized Trial of Zileuton for Treatment of COPD Exacerbations Requiring Hospitalization

Figures & data

Figure 1  Study schematic. If patients remained hospitalized, they were visited as inpatients at the 7-, 14- and 30-day visits.

Figure 2  Consort flow chart.

Table 1  Subject characteristics by intervention group

	n	Placebo	n	Zileuton	p-value
Randomized	59		60
Age	59	64±10	59	62±8	0.20
Men	41	70%	37	63%	0.44
Current smoking	25	42%	21	36%	0.57
Bronchodilators (in past 3 mo, %)	52	88%	52	88%	1.00
Inhaled steroids (in past 3 mo, %)	44	75%	36	61%	0.17
ED visit for COPD (in past 1 yr, %)	24	41%	32	54%	0.16
Hosp visit for COPD (in past yr, %)	30	52%	30	51%	0.92
Oxygen, current (%)	30	51%	27	46%	0.71
Pre-BD FEV1 (L)	13	0.95±0.30	10	0.79±0.49	0.35
Post-BD FEV1 (L)	14	0.86±0.35	15	1.10±0.64	0.21
FEV1 % predicted	28	32±11	25	32±13	0.96
Pre-BD FEV1/FVC (%)	13	40±11	10	45±12	0.41
Post-BD FEV1/FVC (%)	14	48±13	15	45±12	0.53
PackYears	59	58±47	60	52±33	0.43
Race (%)
Caucasian	32	54%	39	66%	NS
African-American	25	42%	17	29%
Asian	1	1%	0	0%
Native-American	3	5%	7	12%
Pacific Islander	0	0%	0	0%
Hispanic	2	3%	4	7%

Data are presented as mean±SD or percentage, BD denotes bronchodilator.

Table 2  Inpatient therapy by visit day

	n	Placebo	n	Zileuton	p-value
Baseline visit (time 0)	59		59
Inhaled beta agonist	57	97%	56	95%	0.65
Inhaled anti-cholinergics	52	88%	52	88%	1.00
Corticosteroids
Oral	26	44%	23	39%	0.58
Parenteral	40	68%	43	73%	0.55
Antibiotics	43	73%	44	75%	0.78
Day 1 visit	54		57
Inhaled beta agonist	50	92%	48	84%	0.17
Inhaled anti-cholinergics	46	85%	46	81%	0.53
Corticosteroids
Oral	25	46%	27	47%	0.91
Parenteral	28	52%	37	65%
Antibiotics	42	78%	43	75%
Day 3 visit	31		32
Inhaled beta agonist	29	94%	28	88%	0.41
Inhaled anti-cholinergics	26	84%	27	84%	0.71
Corticosteroids
Oral	15	48%	19	59%	0.38
Parenteral	15	48%	13	41%	0.54
Antibiotics	25	81%	25	78%	0.81
Day 5 visit	15		12
Inhaled beta agonist	14	93%	11	92%	0.87
Inhaled anti-cholinergics	13	87%	11	92%
Corticosteroids
Oral	8	53%	10	83%	0.68
Parenteral	7	47%	2	16%	0.10
Antibiotics	12	80%	8	67%	0.43

Figure 3  There was no statistically significant difference in hospital length of stay (the primary outcome) between groups (hazard ratio 0.96; 95% confidence interval [95% CI], 0.64–1.42).

Table 3  Treatment failure by intervention group

Treatment failure	Placebo	Zileuton
Death	2	1
Intubation	1	1
Readmission	7	7
Urgent visit	6	7
Intensification of therapy	11	11

Table 4  Spirometric data at the 30-day visit

Post-Bronchodilator spirometry	Placebo n = 32*	Zileuton n = 39*	p-value
FEV1 (L)	1.05±0.47	1.28±0.69	0.11
FEV1 (% predicted)	37.3±15.1	41.6±21.1	0.33
FVC	2.46±0.96	2.59±0.90	0.55
FEV1/FVC	43.6±13.5	47.8±17.8	0.28
GOLD Stage
GOLD I	0	1 (3%)	0.24
GOLD II	5 (15%)	12 (31%)
GOLD III	14 (44%)	10 (25%)
GOLD IV	13 (41%)	16 (41%)

*92 of the 119 participants completed the 30-day visit, and 21 of these 92 did not have spirometry due to refusal, intercurrent illness or because the visit was done by telephone.

Figure 4  Urinary LTE₄ and serum LTB₄ levels. (A) Urinary LTE₄ levels declined with zileuton as compared to placebo at 24 h (p<0.001) and 72 h (p = 0.006). (B) There was no statistically significant difference in the change in serum LTB₄ levels at 30 days between treatment groups (p = 0.19), despite a non-significant decline in geometric mean LTB₄ level of 40% with zileuton.

Table 5  Serious adverse events

	Placebo n = 59	Zileuton n = 60	p-value
Number of SAEs	21	17	0.40
Number of participants having SAEs	18	16	0.64
Number of deaths	3*	1	0.30
Total COPD related SAEs	13	9	0.32
Number of participants with COPD related SAEs	11	8	0.43

*1 respiratory death occurred on day 34 (after the final visit) and therefore is not reflected in study drop-outs.