Role of H2 receptor blocker famotidine over the clinical recovery of COVID-19 patients: A randomized controlled trial

Table 1 Patient demographics, characteristics, and treatment outcomes among the study groups

Variables		Group A (famotidine)	Group B (control)	t-test (95%CI)
Patient demographics and characteristics during hospitalization	Sex	n = 104, male: 78, female: 26	n = 104, male: 77, female: 27
	Age (yr)	57.06 ± 14.97 (23-83)	57.24 ± 13.87 (18-85)	P = 0.92
	Body weight (Kg)	65.9 ± 9.0 (55-93)	66.5 ± 7.7 (53-90)	P = 0.61
	BMI	24.3 ± 5.8 (19.7-35.4)	22.7 ± 5.0 (20.4-34.5)	P = 0.58
	Comorbidity	61 (58.7%)	46 (44.2%)
	Oxygen saturation (%)	85.23 ± 6.961; 73-98	87.77 ± 8.971; 34-99	P = 0.0243a
	PaO2 (mm of Hg)	47.9 ± 6.8; 27-85	52.0 ± 9.8; 28-84	P = 0.005b
	P:F ratio (on admission)	62.9 ± 28.1; 38-210	71.3 ± 35.8; 23-192	P = 0.015a
	Oxygen requirement	19.44 ± 16.56; 4-60 L/min	18.38 ± 10.51; 2-40 L/min	P = 0.643
	CT chest (%)	39.87 ± 14.3; 15-70	27.08 ± 16.7; 15-65	P ≤ 0.0001d
	Respiratory rate	29.07 ± 10; 12-55/min	30.37 ± 6.865; 18-45/min	P = 0.299
	Temperature	100.7 ± 1.865; 98-104 °F	101.4 ± 1.453; 98-104 °F	P = 0.398
	Serum creatinine (mg/dL)	1.2 ± 0.61; 0.5-3.3	1.26 ± 0.62; 0.6-3.5	P = 0.24
	Serum Bilirubin (mg/dL)	1.62 ± 1.0; 0.2-5.0	1.59 ± 1.1; 0.4-5.8	P = 0.80
	Platelet count (103/mL)	206.3 ± 995.2; 85000-400000	221 ± 82.6; 78000-395000	P = 0.24
	MAP (in mm of Hg)	87.0 ± 12.27; 54-116	87.2 ± 11.5; 54-116	P = 0.91
	GCS score	12.1 ± 1.7; 7-15	12.6 ± 1.9; 7-15	P = 0.06
	NEWS-2 score (on admission)	8.3 ± 1.8; 3-12	8.7 ± 2.0; 5-13	P = 0.11
	SOFA day-1 score	6 ± 1.68; 3-11	5.3 ± 1.44; 3-9	P = 0.004b
Characteristics of study group patients during discharge (recovered cases)	NEWS-2 score (on discharge; Recovered cases)	0.89 ± 0.8; 0-2	1.2 ± 0.8; 0-2	P = 0.0221a
	Oxygen saturation (%) (on discharge; Recovered cases)	95.9 ± 2.07; 90-100	96.3 ± 1.5; 93-99	P = 0.080
	Oxygen requirement (on discharge; Recovered cases)	1.36 ± 2.2; 0-10 L/min	1.5 ± 2.4; 0-12 L/min	P = 0.279
	CT chest (%) (on discharge; Recovered cases)	18.0 ± 7.5; 5-35	13.86 ± 9.9; 0-35	P = 0.004b
	Respiratory rate (on discharge; recovered cases)	19.4 ± 4.7; 12-34/min	19.1 ± 2.2; 15-26/min	P = 0.638
	Temperature (on discharge; Recovered cases)	99.9 ± 1.6; 98-104 °F	100.3 ± 1.7; 97.5-103.6 °F	P = 0.252
Treatment outcomes among the study groups	Recovered	n = 78 (75%), male: 58 (74.4%), female 20 (25.6%)	n = 73 (70%), male: 59 (81%), female: 14 (19%)
	Dead	n = 26 (25%), male: 20 (76.9%), female: 6 (23.1%)	n = 31 (30%), male: 18 (58.1%), female: 13 (41.9%)
	Time to clinical improvement	9.53 ± 5.0; 3-27 d	14.21 ± 5.6; 6-28 d	P ≤ 0.0001d
	CT difference (%) (on admission and before discharge)	21.7 ± 9.5; 8-40	13.2 ± 8.9; 0%-40%	P ≤ 0.0001d
	Time to symptomatic recovery	17.9 ± 5.4; 8-37 d	19.3 ± 6.3; 10-35 d	P = 0.14
	duration of ICU stay	9.28 ± 4.96; 1-27 d	10.23 ± 7.13; 2-42 d	P = 0.26
	Total duration of hospitalization	11.73 ± 6.0; 1-30 d	14.13 ± 7.6; 3-42 d	P = 0.013a
	Duration of hospitalization (recovered patients)	13.04 ± 5.5; 4-30 d	16.31 ± 6.1; 7-30 d	P = 0.0009c
	Duration of ICU stay (recovered patients)	9.7 ± 4.6; 1-26 d	10.6 ± 6.3; 2-26 d	P = 0.33
	Time to clinical failure/death	6.9 ± 6.1; 1-27 d	10.4 ± 12.2; 3-42 d	P = 0.1986
	Time to viral clearance (negative PCR)	20.7 ± 5.9; 13-39 d	23.8 ± 6.4; 13-42 d	P = 0.002b

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

^dP ≤ 0.0001.

BMI: Body mass index; CT: Computed tomography; MAP: Mean arterial pressure; GCS: Glasgow coma scale; NEWS-2: National early warning score-2; SOFA: Sequential organ failure assessment; ICU: Intensive care unit; PCR: Polymerase chain reaction.

Table 2 Subgroup analysis according to sex and duration

Variables	Duration	Male (%)		Female (%)
Group A, ICU stay	< 10 d (71)	51 (65.3)	n = 78	20 (76.9)	n = 26
	11-20 d (30)	24 (30.76)		6 (23.1)
	21-30 d (3)	3 (3.8)		0 (0)
	≥ 31 d (0)	0 (0)		0 (0)
Group B, ICU stay	≤ 10 d (68)	55 (69.6)	n = 79	13 (52)	n = 25
	11-20 d (25)	16 (20.2)		9 (36)
	21-30 d (9)	8 (10.1)		1 (4)
	≥ 31 d (2)	0 (0)		2 (8)
Group A (n = 101), duration of total hospital stays	≤ 10 d (51)	37 (47.4)	n = 78	14 (53.8)	n = 26
	11-20 d (43)	33 (42.3)		10 (38.5)
	21-30 d (10)	8 (10.3)		2 (7.7)
	≥ 31 d (0)	0 (0)		0 (0)
Group B (n = 104), duration of total hospital stays	≤ 10 d (40)	31 (39.2)	n = 79	9 (36)	n = 25
	11-20 d (49)	40 (50.6)		9 (36)
	21-30 d (13)	8 (10.1)		5 (20)
	≥ 31 d (2)	0 (0)		2 (8)
Group A (n = 78), time to clinical improvement	≤ 10 d (50)	31 (55.4)	n = 56	19 (86.3)	n = 22
	11-20 d (24)	21 (37.5)		3 (13.6)
	21-30 d (4)	4 (7.1)		0 (0)
Group B (n = 73), time to clinical improvement	≤ 10 d (21)	20 (32.7)	n = 61	1 (8.3)	n = 12
	11-20 d (41)	34 (55.7)		7 (58.3)
	21-30 d (11)	7 (11.4)		4 (33.3)
Group A (n = 78), recovered cases, duration of ICU stay	≤ 10 d (49)	33 (59)	n = 56	16	n = 22
	11-20 d (27)	21 (37.5)		6
	21-30 d (2)	2 (3.5)		0
	≥ 31 d (0)	0 (0)		0
Group B (n = 73), recovered cases, duration of ICU stay	≤ 10 d (41)	37 (60)	n = 61	4 (33.3)	n = 12
	11-20 d (24)	16 (17)		8 (66.6)
	21-30 d (8)	8 (13)		0 (0)
	≥ 31 d (0)	0 (0)		0 (0)
Group A (n = 26), expired cases; Time to clinical failure/death	≤ 10 d (1)	1 (4.5)	n = 22	0 (0)	n = 4
	11-20 d (22)	18 (82)		4 (100)
	21-30 d (3)	3 (13.5)		0 (0)
Group B (n = 31), expired cases, time to clinical failure/death	≤ 10 d (27)	18 (100)	n = 18	9 (70)	n = 13
	11-20 d (1)	0 (0)		1 (7.5)
	21-30 d (1)	0 (0)		1 (7.5)
	> 31 d (2)	0 (0)		2 (15)
Group A (survived patients) (n = 78), time to symptomatic recovery	< 10 d (21)	20 (32.8)	n = 61	1 (8.3)	n = 12
	11-20 d (41)	34 (55.7)		7 (58.3)
	21-30 d (11)	7 (11.5)		4 (33.3)
	> 31 d (0)	0 (0)		0 (0)
Group B (survived patients) (n = 73), time to symptomatic recovery	< 10 d (3)	3 (3.91)	n = 61	0 (0)	n = 12
	11-20 d (45)	41 (67.2)		4 (33.3)
	21-30 d (19)	12 (19.7)		7 (58.3)
	>31 d (6)	5 (8.1)		1 (8.3)
Group A (n = 78) time to negative PCR recovery	11-20 d (41)		n = 56		n = 22
	21-30 d (32)
	31-40 d (5)
Group B (survived patients) (n = 73), time to negative PCR recovery	11-20 d (26)		n = 61		n = 12
	21-30 d (35)
	31-40 d (12)
Group A (n = 78), CT chest involvement on admission	< 20%	26 (46.4)	n = 56	15 (68.2)	n = 22
	21%-40%	16 (28.6)		5 (22.7)
	41%-60%	11 (19.6)		2 (9.0)
	> 61%	3 (5.3)		0 (0)
Group B (n = 73), CT chest involvement on admission	< 20	26 (42.6)	n = 61	3 (25)	n = 12
	21-40	22 (36)		7 (58.3)
	41-60	13 (21.3)		1 (8.3)
	> 61	0 (0)		1 (8.3)
Group A (n = 78), CT chest involvement during discharge	< 20	47 (83.9)	n = 56	16 (72.7)	n = 22
	21-40	9 (16)		6 (12.2)
Group B (n = 73), CT chest involvement during discharge	< 20	47 (77)	n = 61	8 (36.4)	n = 12
	21-40	14 (23)		4 (33.3)
Group A (n = 78), chest CT improvement	< 20	44 (74.6)	n = 56	19 (86.6)	n = 22
	21-40	5 (8.5)		3 (13.6)
	41-60	7 (11.9)		0 (0)
Group B (n = 73), CT improvement	< 20	54 (88.5)	n = 61	10 (83.3)	n = 12
	21-40	4 (6.6)		1 (8.3)
	41-60	3 (4.9)		1 (8.3)

ICU: Intensive care unit; CT: Computed tomography.

Table 3 Analysis of the total duration of hospitalization and intensive care unit stay against the age group

Variables	Age group (yr)	Group A (famotidine)				Group B (control)
		1-10 d	11-20 d	21-30 d	> 31 d	1-10 d	11-20 d	21-30 d	> 31 d
Duration of hospital stay, group A (n = 104), group B (n = 104)	11-20	1	1	0	0	4	0	0	0
	21-30	1	1	0	0	8	8	0	0
	31-40	4	5	0	0	12	8	0	0
	41-50	7	8	1	0	4	8	4	0
	51-60	18	11	5	0	0	17	5	2
	61-70	11	10	4	0	12	4	4	0
	71-80	6	6	0	0	0	4	0	0
	> 81	3	1	0	0	4	0	0	0
Total (%)		51 (49)	43 (41.5)	10 (9.5)	0 (0)	40 (38.5)	49 (47.1)	13 (12.5)	2 (1.9)
Duration of ICU stay, group A (n = 104), group B (n = 104)	11-20	2	0	0	0	4	0	0	0
	21-30	2	0	0	0	12	4	0	0
	31-40	6	3	0	0	20	0	0	0
	41-50	8	8	0	0	12	0	4	0
	51-60	23	10	1	0	8	13	1	2
	61-70	17	6	2	0	12	4	4	0
	71-80	9	3	0	0	0	4	0	0
	> 81	4	0	0	0	4	0	0	0
Total (%)		71 (68)	30 (29)	3 (3)	0 (0)	68 (65.4)	25 (24)	9 (8.6)	2 (1.9)

ICU: Intensive care unit.

Table 4 Subgroup analysis of the study group patients depending on age group

Age group (yr)	Total study population (%)	Over all (%)		Recovered patients (%)		Death cases (%)
		Group A	Group B	Group A	Group B	Group A	Group B
11-20	2 (1)	2 (2)	0 (0)	2 (2.5)	0 (0)	0 (0)	0 (0)
21-30	6 (2.9)	2 (2)	4 (4)	2 (2.5)	0 (0)	0 (0)	4 (13)
31-40	25 (12)	9 (8.5)	16 (16)	8 (10)	16 (22)	1 (4)	0 (0)
41-50	36 (17.3)	16 (15)	20 (19)	9 (11.5)	8 (11)	7 (27)	12 (39)
51-60	50 (24)	34 (33)	16 (15)	24 (31)	16 (22)	10 (38)	0 (0)
61-70	49 (23.6)	25 (24)	24 (23)	19 (24.5)	20 (27)	6 (23)	4 (13)
71-80	32 (15.4)	12 (11.5)	20 (19)	10 (13)	9 (12)	2 (8)	11 (35)
> 81	8 (3.8)	4 (4)	4 (4)	4 (5)	4 (6)	0 (0)	0 (0)
Total	208	104	104	78	73	26	31

Table 5 Analysis of the hospital stay, intensive care unit stay, time to symptomatic recovery, and time to negative polymerase chain reaction among the recovered patients against duration and age

Variables	Age group (yr)	Group A (famotidine)					Group B (control)
		1-10 d	11-20 d	21-30 d	> 31 d	Total	1-10 d	11-20 d	21-30 d	> 31 d	Total
Duration of hospital stay (recovered cases), group A (n = 78), group B (n = 73)	11-20	0	2	0	0	2	0	0	0	0	0
	21-30	0	1	1	0	2	0	0	0	0	0
	31-40	3	4	1	0	8	8	8	0	0	16
	41-50	4	5	0	0	9	0	8	0	0	8
	51-60	13	8	3	0	24	4	8	4	0	16
	61-70	5	13	1	0	19	0	16	4	0	20
	71-80	5	4	1	0	10	1	4	4	0	9
	> 81	1	2	1	0	4	0	4	0	0	4
Total (%)		31 (40)	39 (50)	8 (10)	0 (0)	78 (100)	13 (18)	48 (66)	12 (16)	0 (0)	73 (100)
Duration of ICU stay (recovered cases), group A (n = 78), group B (n = 73)	11-20	2	0	0	0	2	0	0	0	0	0
	21-30	1	1	0	0	2	0	0	0	0	0
	31-40	6	2	0	0	8	12	4	0	0	16
	41-50	5	4	0	0	9	8	0	0	0	8
	51-60	20	4	0	0	24	12	0	4	0	16
	61-70	8	11	0	0	19	8	12	0	0	20
	71-80	6	3	1	0	10	1	4	4	0	9
	> 81	1	2	1	0	4	0	4	0	0	4
Total (%)		49 (63)	27 (34.5)	2 (2.5)	0 (0)	78 (100)	41 (56)	24 (33)	8 (11)	0 (0)	73 (100)
Duration of hospital/ICU stay (death cases), group A (n = 26), group B (n = 32)	11-20	0	0	0	0	0	0	0	0	0	0
	21-30	0	0	0	0	0	4	0	0	0	4
	31-40	0	1	0	0	1	0	0	0	0	0
	41-50	0	7	0	0	7	12	0	0	0	12
	51-60	1	8	1	0	10	0	0	0	0	0
	61-70	0	4	2	0	6	0	1	1	2	4
	71-80	0	2	0	0	2	11	0	0	0	11
	> 81	0	0	0	0	0	0	0	0	0	0
Total (%)		1 (4)	22 (84.5)	3 (11.5)	0 (0)	26 (100)	27 (88)	1 (3)	1 (3)	2 (6)	31 (100)
Time to clinical improvement (recovered cases), group A (n = 78), group B (n = 73)	11-20	2	0	0	0	2	0	0	0	0	0
	21-30	1	1	0	0	2	0	0	0	0	0
	31-40	6	2	0	0	8	3	10	3	0	16
	41-50	5	3	1	0	9	2	3	3	0	8
	51-60	17	6	1	0	24	7	9	0	0	16
	61-70	10	8	1	0	19	6	11	3	0	20
	71-80	5	4	1	0	10	2	6	1	0	9
	> 81	4	0	0	0	4	1	2	1	0	4
Total (%)		50 (64)	24 (31)	4 (5)	0 (0)	78 (100)	21 (29)	41 (56)	11 (15)	0 (0)	73 (100)
Time to negative PCR (recovered cases), group A (n = 78), group B (n = 73)	11-20	0	2	0	0	2	0	0	0	0	0
	21-30	0	0	2	0	2	0	0	0	0	0
	31-40	0	7	1	0	8	0	9	7	0	16
	41-50	0	7	1	1	9	0	4	4	0	8
	51-60	0	12	11	1	24	0	8	5	3	16
	61-70	0	6	12	1	19	0	4	11	5	20
	71-80	0	4	5	1	10	0	1	4	4	9
	> 81	0	3	0	1	4	0	0	4	0	4
Total (%)		0 (0)	41 (53)	32 (41)	5 (6)	78 (100)	0 (0)	26 (36)	35 (48)	12 (16)	73 (100)
Time to symptomatic improvement (recovered cases), group A (n = 78), group B (n = 73)	11-20	0	2	0	0	2	0	0	0	0	0
	21-30	0	2	0	0	2	0	0	0	0	0
	31-40	2	6	0	0	8	2	13	1	0	16
	41-50	4	4	1	0	9	0	6	2	0	8
	51-60	11	12	1	0	24	1	11	3	1	16
	61-70	7	11	1	0	19	0	11	8	1	20
	71-80	3	7	0	0	10	0	3	2	4	9
	> 81	1	3	0	0	4	0	1	3	0	4
Total (%)		28 (36)	47 (60)	3 (4)	0 (0)	78 (100)	3 (4)	45 (62)	19 (26)	6 (82)	73 (100)

ICU: Intensive care unit; PCR: Polymerase chain reaction.

Table 6 Distribution of comorbidity among the study groups

Comorbidity, n (%)	Group A, n (%): Male 46 (75.4), female 15 (24.59)					Group B n (%): Male 33 (71.7), female 13 (28.3)
	Total 61 (58.7)	Recovered cases 21 (34.42)		Death cases 15 (24.59)		Total 46 (44.2)	Recovered cases 24 (52.1)		Death cases 10 (21.7)
		≥ 2 (12)	< 2 (9)	≥ 2 (12)	< 2 (3)		≥ 2 (10)	< 2 (14)	≥ 2 (8)	< 2 (2)
HTN, 22 (19)	16 (15.8)	6 (50)	5 (55.5)	5 (50)	0	22 (21.1)	8 (44.4)	6 (42.8)	7 (87.5)	1 (50)
IHD, 11 (5.5)	8 (7.9)	3 (25)	0	4 (33.3)	1 (33.3)	3 (2.8)	1 (10)	2 (14.2)	0	0
Diabetes mellitus, 28 (14)	15 (14.5)	6 (50)	1 (11.1)	8 (66.6)	0	13 (12.5)	5 (27.8)	1 (7.1)	6 (75)	1 (50)
COPD	5 (4.8)	1 (8.3)	1 (11.1)	3 (25)	0	4 (3.9)	3 (30)	1 (7.1)	0	0
BPH	9 (8.9)	5 (41.6)	0	2 (16.6)	2 (66.6)	3 (2.8)	1 (10)	0	2 (25)	0
Rheumatoid arthritis	4 (3.8)	4 (33.3)	0	0	0	2 (1.9)	1 (10)	1 (7.1)	0	0
Osteoarthritis	5 (4.8)	1 (8.3)	3 (33.3)	0	1 (33.3)	1 (0.9)	0	1 (7.1)	0	0
Hypothyroid	3 (2.9)	2 (16.6)	1 (11.1)	0	0	1 (0.9)	0	1 (7.1)	0	0
Ischemic stroke	2 (1.9)	1 (8.3)	1 (11.1)	0	0	1 (0.9)	0	1 (7.1)	0	0
Heart failure	2 (1.9)	1 (8.3)	0	1 (8.3)	0	2 (1.9)	0	0	2	0
Chronic kidney disease	1 (1)	0	0	0	1 (33.3)	1 (0.9)	0	1 (7.1)	0	0
Bronchial asthma	1 (1)	1 (8.3)	0	0	0	2 (1.9)	0	0	2 (25)	0
IBD	1 (1)	0	0	0	1 (33.3)	0 (0)	0	0	0	0
IBS	0	0	0	0	0	1 (0.9)	0	1 (7.1)	0	0
Hepatitis B	1 (1)	0	1 (8.3)	0	0	1 (0.9)	0	1 (7.1)	0	0
Migraine	1 (1)	1 (8.3)	0	0	0	3 (2.8)	0	1 (7.1)	2 (25)	0
Carcinoma (early)	1 (1)	1 (8.3)	0	0	0	0	0	0	0	0

HTN: hypertension; IHD: Ischemic heart disease; COPD: Chronic obstructive pulmonary disease; BPH: Benign prostatic hyperplasia; IBD: Inflammatory bowel disease; IBS: Irritable bowel syndrome.