Comparison of the prophylactic antithrombotic effect of indobufen and warfarin in patients with nephrotic syndrome: a randomized controlled trial

Figures & data

Figure 1. Flow chart for the study population.

Table 1. Baseline characteristics of enrolled patients.^a

Variables	Indobufen, 100 mg*2/d (n = 59)	Indobufen, 200 mg*2/d (n = 61)	Warfarin, INR 1.5–3.0 (n = 60)^b	p Value
Age (years, mean ± SD)	47.3 ± 16.7	44.3 ± 15.7	45.5 ± 16.9	.601
Male sex, n (%)	42 (71.2%)	37 (60.7%)	32 (53.3%)	.132
Weight (kg, mean ± SD)	72.1 ± 14.2	69.0 ± 11.4	66.5 ± 14.6	.076
Body-mass index (kg/m^2)	25.5 ± 4.2	24.9 ± 3.2	24.3 ± 4.0	.215
Pathological type, n (%)				.107
MN	35 (59.3%)	30 (49.2%)	32 (51.7%)
IgAN	2 (3.4%)	6 (9.8%)	10 (16.7%)
MCD	8 (13.6%)	8 (13.1%)	11 (18.3%)
Other	8 (13.6%)	14 (23.0%)	5 (8.3%)
Unknow	6 (10.2%)	3 (4.9%)	2 (3.3%)
Laboratory test
Hb (g/L)	130.70 ± 29.81	134.26 ± 20.71	126.50 ± 25.71	.251
PLT (10^9/L)	241.07 ± 77.77	244.45 ± 76.02	245.03 ± 61.60	.950
SAlb (g/L)	23.75 ± 7.52	23.26 ± 6.34	23.27 ± 7.11	.911
BUN (mmol/L)	5.4 (4.0, 6.8)	5.4 (4.2, 7.2)	5.9 (4.8, 7.5)	.210
SCr (μmol/L)	75.0 (61.3, 85.4)	73.0 (59.3, 87.2)	67.9 (57.9, 81.6)	.220
APTT (s)	27.66 ± 9.30	27.25 ± 8.63	27.32 ± 10.29	.969
PT (s)	11.5 (10.6, 12.4)	11.1 (10.3, 12.4)	11.6 (10.5, 12.3)	.649
TT (s)	18.12 ± 1.54	18.30 ± 1.41	18.48 ± 2.31	.573
FIB (g/L)	4.6 (3.7, 5.5)	4.2 (3.1, 5.4)	3.9 (3.5, 4.8)	.103
D-dimer (μg/L)	3780 (1325, 4883)	3210 (1710, 4855)	3675 (1727, 4600)	.695
INR	0.89	NA	0.96 ± 0.22	NA

Note: APTT: activated partial thromboplastin time; BUN: blood urea nitrogen; FIB: fibrinogen; Hb: hemoglobin; IgAN: Immunoglobulin A nephropathy; MCD: minimal change disease; MN: membranous nephropathy; PLT: platelet; PT: prothrombin time; SAlb: serum albumin; SCr: serum creatinine; TT: thrombin time.

^a The analysis of the baseline data was performed in the intention-to-treat set (n = 180).

^b 3 mg/d at day 1, dose adjustment was based on INR.

Table 2. Clinical outcomes (n = 180).^a

Variables	Indobufen, 100 mg*2/d (n = 59)	Indobufen, 200 mg*2/d (n = 61)	Warfarin, INR 1.5–3.0 (n = 60)	p Value
Efficacy, n (%)
Thromboembolic events	0	0	0	ns
Safety, n (%, 95%CI)^b
Bleeding events	1 (2%, 0–5)^c	3 (5%, 0–11)	11 (18%, 6–30)	.013
Non-glomerular hematuria	0	2	3
Gastrointestinal bleeding	0	0	1
Subcutaneous bleeding	1	1	3
Submucosal hemorrhage	0	0	1
Subconjunctival bleeding	0	0	1
Nasal bleeding	0	0	1
Gum hemorrhage	0	0	1

^a The analysis of efficacy and safety outcomes were performed in the intention-to-treat set (n = 180).

^b 95% CI of proportions were calculated with the Wilson’s score method. Patients with more than one bleeding event in one same place were only counted once.

^c p < .05 compared with warfarin group.

Table 3. Laboratory analysis.

Variables	Timepoints	Indobufen, 100 mg*2/d (n = 59)	Indobufen, 200 mg*2/d (n = 61)	Warfarin, INR 1.5–3.0 (n = 60)	p Value
APTT (s)	Baseline	27.66 ± 9.30	27.25 ± 8.63	27.32 ± 10.29	.969
	4 weeks	24.79 ± 7.74	25.10 ± 7.31	35.81 ± 11.15	<.001
	8 weeks	23.45 ± 7.32	22.92 ± 7.11	31.46 ± 10.27	<.001
	12 weeks	25.53 ± 6.56	24.52 ± 7.52	28.99 ± 7.97	.010
PT (s)	Baseline	12.73 ± 4.88	12.62 ± 4.52	13.15 ± 4.80	.813
	4 weeks	12.78 ± 5.69	11.79 ± 4.04	26.72 ± 10.19	<.001
	8 weeks	12.44 ± 5.12	11.94 ± 4.17	21.23 ± 9.85	<.001
	12 weeks	12.48 ± 5.61	11.72 ± 3.93	19.07 ± 7.87	<.001
TT (s)	Baseline	18.12 ± 1.54	18.30 ± 1.41	18.48 ± 2.31	.573
	4 weeks	18.40 ± 1.65	19.03 ± 1.95	17.97 ± 1.58	.008
	8 weeks	17.48 ± 1.45	17.41 ± 1.42	17.46 ± 2.59	.979
	12 weeks	17.62 ± 1.48	19.82 ± 16.85	17.61 ± 2.10	.471
D-dimer (μg/L)	Baseline	3985.18 ± 3340.52	3717.67 ± 3302.78	3439.00 ± 1930.44	.603
	4 weeks	3070.04 ± 2021.52	3481.56 ± 2563.87	3069.02 ± 1879.85	.557
	8 weeks	2929.25 ± 1979.59	3265.00 ± 4105.18	2915.60 ± 2151.31	.783
	12 weeks	2506.67 ± 1795.17	2845.33 ± 2301.67	2610.89 ± 2045.67	.734
INR	Baseline	0.89±…	NA	0.96 ± 0.22	…
	4 weeks	NA	NA	1.87 ± 0.92	…
	8 weeks	0.90±…	NA	1.66 ± 0.72	…
	12 weeks	NA	1.02±…	1.52 ± 0.60	…

Note: APTT: activated partial thromboplastin time; PT: prothrombin time; TT: thrombin time.

Table 4. Adverse events (n = 180).

Events	Indobufen, 100 mg*2/d (n = 59)	Indobufen, 200 mg*2/d (n = 61)	Warfarin, INR 1.5–3.0 (n = 60)
Erythra	0	0	1
Cough	1	1	0
Headache	0	0	1
Hand twitch	0	1	0
Dry mouth	0	0	1
Abdominal distension	0	0	1
Diarrhea	0	0	1
Nausea	0	1	0
Sudden cardiac death	0	0	1
New onset tumor	1	1	0

Data availability statement

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.