Systematic review of topical treatments for fungal infections of the skin and nails of the feet -- Hart et al. 319 (7202): 79 Data Supplement - tables A

Table A Placebo controlled trials of topical azoles for fungal skin infections of foot

Table B Placebo controlled trials of allylamines and other topical treatments for fungal skin infections of foot

Table C Comparative trials of two active topical treatments for fungal infections of skin or nails of foot

Table D Comparative trials of more than two active topical treatments for fungal skin infections of foot

Table A Placebo controlled trials of topical azoles for fungal skin infections of foot

Trial	Interventions	Sample size	Treatment (weeks)	Follow up (weeks)	% Cure rate (No cured)	% Difference in risk (95% CI)	Relative risk (95% CI)
Bagatell (1986)^w1	Bifonazole	26	4	6	73 (19)	25 (-3 to 51)	0.65 (0.37 to 1.04)
Bagatell (1986)^w1	Placebo	21	4	6	48 (10)	25 (-3 to 51)	0.65 (0.37 to 1.04)
Coffey (1986)^w12	Bifonazole	16	4	6	100 (16)	71 (45 to 88)	0.29 (0.12 to 0.57)
Coffey (1986)^w12	Placebo	14	4	6	29 (4)	71 (45 to 88)	0.29 (0.12 to 0.57)
Izuno (1986)^w13	Bifonazole	20	4	6	90 (18)	23 (-3 to 49)	0.74 (0.48 to 1.04)
Izuno (1986)^w13	Placebo	18	4	6	67 (12)	23 (-3 to 49)	0.74 (0.48 to 1.04)
Smith (1986)^w14	Bifonazole	23	4	6	91 (21)	69 (45 to 83)	0.25 (0.12 to 0.45)
Smith (1986)^w14	Placebo	31	4	6	23 (7)	69 (45 to 83)	0.25 (0.12 to 0.45)
Speikerman I (1976)^w120	Clotrimazole	133	6	6	78 (104)	32 (21 to 42)	0.59 (0.48 to 0.72)
Speikerman I (1976)^w120	Placebo	134	6	6	46 (62)	32 (21 to 42)	0.59 (0.48 to 0.72)
Speikerman II (1976)^w120	Clotrimazole	17	6	6	88 (15)	59 (30 to 78)	0.33 (0.17 to 0.59)
Speikerman II (1976)^w120	Placebo	24	6	6	29 (7)	59 (30 to 78)	0.33 (0.17 to 0.59)
Smith (1977)^w121	Clotrimazole	33	6	6	67 (22)	27 (3 to 48)	0.59 (0.35 to 0.94)
Smith (1977)^w121	Placebo	33	6	6	39 (13)	27 (3 to 48)	0.59 (0.35 to 0.94)
Daily (1985)^w15	Econazole	32	4	8	97 (31)	14 (-3 to 42)	0.86 (0.57 to 1.04)
Daily (1985)^w15	Placebo	12	4	8	83 (10)	14 (-3 to 42)	0.86 (0.57 to 1.04)
Ison (1990)^w16	Econazole	19	4	8	100 (19)	54 (29 to 77)	0.46 (0.25 to 0.83)
Ison (1990)^w16	Placebo	13	4	8	46 (6)	54 (29 to 77)	0.46 (0.25 to 0.83)
Mandy (1974)^w19	Miconazole	6	4	8	100 (6)	0 (-41 to 41)	1.00 (0.57 to 1.74)
Mandy (1974)^w19	Placebo	6	4	8	100 (6)	0 (-41 to 41)	1.00 (0.57 to 1.74)
Duncan (1975)^w17	Miconazole	49	4	8	90 (44)	51 (34 to 64)	0.44 (0.30 to 0.60)
Duncan (1975)^w17	Placebo	56	4	8	39 (22)	51 (34 to 64)	0.44 (0.30 to 0.60)
Gentles (1975)^w18	Miconazole	10	4	8	70 (7)	3 (-49 to 40)	0.95 (0.40 to 1.89)
Gentles (1975)^w18	Placebo	6	4	8	67 (4)	3 (-49 to 40)	0.95 (0.40 to 1.89)
Ortiz (1978)^w20	Miconazole	50	4	8	94 (47)	76 (61 to 86)	0.19 (0.10 to 0.33)
Ortiz (1978)^w20	Placebo	50	4	8	18 (9)	76 (61 to 86)	0.19 (0.10 to 0.33)
Akers (1989)^w122	Sulconazole	62	4	6	82 (51)	48 (28 to 65)	0.42 (0.25 to 0.64)
Akers (1989)^w122	Placebo	32	4	6	34 (11)	48 (28 to 65)	0.42 (0.25 to 0.64)
Smith (1988)^w124	Tioconazole	14	6	10	86 (12)	-14 (-41 to 33)	1.50 (0.71 to 1.93)
Smith (1988)^w124	Placebo	5	6	10	100 (5)	-14 (-41 to 33)	1.50 (0.71 to 1.93)

Table B Placebo controlled trials of allylamines and other topical treatments for fungal skin infections of foot

Trial	Interventions	Sample size	Treatment (weeks)	Follow up (weeks)	% Cure rate (No cured)	% Difference in risk (95% CI)	Relative risk (95% CI)
Allylamines
Savin (1997)^w22	Butenafine	132	1	6	74 (98)	52 (41 to 61)	0.30 (0.22 to 0.41)
Savin (1997)^w22	Placebo	139	1	6	22 (31)	52 (41 to 61)	0.30 (0.22 to 0.41)
Tschen (1997)^w23	Butenafine	40	4	8	88 (35)	55 (35 to 70)	0.37 (0.23 to 0.56)
Tschen (1997)^w23	Placebo	40	4	8	33 (13)	55 (35 to 70)	0.37 (0.23 to 0.56)
Klaschka (1984)^w4	Naftifine	29	4	6	100 (29)	96* (81 to 99)	0.02* (0.00 to 0.17)
Klaschka (1984)^w4	Placebo	24	4	6	0 (0)	96* (81 to 99)	0.02* (0.00 to 0.17)
Dobson (1989)^w3	Naftifine	95	4	6	66 (63)	48 (35 to 60)	0.27 (0.17 to 0.43)
Dobson (1989)^w3	Placebo	88	4	6	18 (16)	48 (35 to 60)	0.27 (0.17 to 0.43)
Schachner (1990)^w5	Naftifine	47	4	6	62 (29)	32 (12 to 50)	0.48 (0.28 to 0.77)
Schachner (1990)^w5	Placebo	44	4	6	29 (13)	32 (12 to 50)	0.48 (0.28 to 0.77)
Bagatell I (1991)^w1	Naftifine	42	4	6	50 (21)	35 (16 to 52)	0.30 (0.14 to 0.62)
Bagatell I (1991)^w1	Placebo	46	4	6	15 (7)	35 (16 to 52)	0.30 (0.14 to 0.62)
Bagatell II (1991)^w1	Naftifine	117	4	6	73 (85)	56 (44 to 66)	0.24 (0.15 to 0.35)
Bagatell II (1991)^w1	Placebo	111	4		17 (19)	56 (44 to 66)	0.24 (0.15 to 0.35)
Savin (1990)^w8	Terbinafine	9	4	6	67 (6)	63* (35 to 88)	0.06* (0.01 to 0.47)
Savin (1990)^w8	Placebo	13	4	6	0 (0)	63* (35 to 88)	0.06* (0.01 to 0.47)
Smith (1990)^w10	Terbinafine	9	4	6	78 (7)	73* (38 to 94)	0.07* (0.01 to 0.52)
Smith (1990)^w10	Placebo	9	4	6	0 (0)	73* (38 to 94)	0.07* (0.01 to 0.52)
Evans (1991)^w7	Terbinafine	27	2	6	81 (22)	36 (9 to 60)	0.55 (0.31 to 0.87)
Evans (1991)^w7	Placebo	20	2	6	45 (9)	36 (9 to 60)	0.55 (0.31 to 0.87)
Berman (1992)^w6	Terbinafine	80	1	6	88 (70)	65 (51 to 75)	0.26 (0.17 to 0.38)
Berman (1992)^w6	Placebo	79	1	6	23 (18)	65 (51 to 75)	0.26 (0.17 to 0.38)
Savin (1994)^w9	Terbinafine	97	2	8	69 (67)	54 (42 to 65)	0.21 (0.13 to 0.34)
Savin (1994)^w9	Placebo	96	2	8	14 (13)	54 (42 to 65)	0.21 (0.13 to 0.34)
Other
Kligman I (1985)^w2	Ciclopiroxolamine	71	4	6	56 (40)	48 (35 to 61)	0.14 (0.06 to 0.31)
Kligman I (1985)^w2	Placebo	73	4	6	8 (6)	48 (35 to 61)	0.14 (0.06 to 0.31)
Aly (1994)^w123	Griseofulvin	47	4	6	81 (38)	46 (29 to 64)	0.42 (0.27 to 0.64)
Aly (1994)^w123	Placebo	47	4	6	34 (16)	46 (29 to 64)	0.42 (0.27 to 0.64)
Gomez (1986)^w21	Tolciclate	11	6	8	82 (9)	15 (-29 to 67)	0.81 (0.25 to 1.50)
Gomez (1986)^w21	Placebo	3	6	8	67 (2)	15 (-29 to 67)	0.81 (0.25 to 1.50)
Chretien (1980)^w24	Undecenoic acid and zinc undeceonate	23	4	6	87 (20)	64 (37 to 81)	0.26 (0.12 to 0.52)
Chretien (1980)^w24	Placebo	22	4	6	23 (5)	64 (37 to 81)	0.26 (0.12 to 0.52)

*When observed number of cures or failures is zero, both difference in risk and relative risk estimated by replacing zero with 0.5, a form of "continuity correction."^w117

Table C Comparative trials of two active topical treatments for fungal infections of skin or nails of foot

Trial	Interventions	Sample size	Treatment (weeks)	Follow up (weeks)	% Cure rate (No cured)	% Difference in risk (95% CI)	Relative risk (95%CI)
Comparison of allylamines v azoles in fungal infections of skin
Del Palacio (1989)^w29	Amorolfine	6	6	3	100 (6)	0 (-41 to 59)	1.00 (0.38 to 1.66)
Del Palacio (1989)^w29	Bifonazole	3	6	3	100 (3)	0 (-41 to 59)	1.00 (0.38 to 1.66)
Bojanovsky (1985^w27	Naftifine	49	5	5	84 (41)	-6 (-20 to 7)	1.08 (0.72 to 1.29)
Bojanovsky (1985^w27	Bifonazole	50	5	5	91 (45)	-6 (-20 to 7)	1.08 (0.72 to 1.29)
Haas (1985)^w38	Naftifine	99	4	4	88 (87)	8 (-2 to 18)	0.91 (0.80 to 1.03)
Haas (1985)^w38	Clotrimazole	105	4	4	81 (84)	8 (-2 to 18)	0.91 (0.80 to 1.03)
Kagawa (1985)^w39	Naftifine	78	5	5	72 (56)	30 (15 to 44)	0.58 (0.47 to 0.71)
Kagawa (1985)^w39	Clotrimazole	77	5	5	42 (32)	30 (15 to 44)	0.58 (0.47 to 0.71)
Plotkin (1990)^w40	Naftifine	30	4	6	40 (12)	3 (-22 to 27)	0.93 (0.48 to 1.77)
Plotkin (1990)^w40	Clotrimazole	27	4	6	37 (10)	3 (-22 to 27)	0.93 (0.48 to 1.77)
Smith (1992)^w36	Naftifine	72	4	8	74 (53)	29 (13 to 43)	0.61 (0.45 to 0.80)
Smith (1992)^w36	Clotrimazole	74	4	8	45 (33)	29 (13 to 43)	0.61 (0.45 to 0.80)
Evans (1993a)^w37	Naftifine	33	4	12	94 (31)	7 (-9 to 27)	0.93 (0.72 to 1.11)
Evans (1993a)^w37	Clotrimazole + hydrocortisone	23	4	12	87 (20)	7 (-9 to 27)	0.93 (0.72 to 1.11)
Sanchez (1994)^w32	Terbinafine	16	4	4	19 (3)	-37 (-6 to –60)	2.96 (1.17 to 8.78)
Sanchez (1994)^w32	Bifonazole	27	4	4	56 (15)	-37 (-6 to –60)	2.96 (1.17 to 8.78)
Evans (1993b)^w31	Terbinafine	107	1	6	97 (104)	14 (6 to 22)	0.86 (0.77 to 0.93)
Evans (1993b)^w31	Clotrimazole	104	4	6	84 (87)	14 (6 to 22)	0.86 (0.77 to 0.93)
Vermeer (1996)^w33	Terbinafine	102	1	6	95 (97)	-2 (-8 to 5)	1.02 (0.95 to 1.09)
Vermeer (1996)^w33	Miconazole	89	4	6	97 (86)	-2 (-8 to 5)	1.02 (0.95 to 1.09)
Comparison between two azoles in fungal infections of skin
Qadripur (1979)^w34	Econazole	30	4	4	67 (20)	30 (5 to 54)	0.55 (0.32 to 0.93)
Qadripur (1979)^w34	Clotrimazole	30	4	4	37 (11)	30 (5 to 54)	0.55 (0.32 to 0.93)
Fredriksson (1982)^w25	Bifonazole	10	3	5	70 (7)	50 (5 to 78)	0.29 (0.08 to 0.87)
Fredriksson (1982)^w25	Econazole	10	3	5	20 (2)	50 (5 to 78)	0.29 (0.08 to 0.87)
Privat (1982)^w26	Bifonazole	20	3	5	75 (15)	5 (-23 to 33)	0.93 (0.63 to 1.37)
Privat (1982)^w26	Econazole	20	3	5	70 (14)	5 (-23 to 33)	0.93 (0.63 to 1.37)
Tanenbaum (1982)^w42	Sulconazole	6	4	10	100 (6)	0 (-41 to 46)	1.00 (0.52 to 1.72)
Tanenbaum (1982)^w42	Miconazole	5	4	10	100 (5)	0 (-41 to 46)	1.00 (0.52 to 1.72)
Roberts (1985)^w47	Bifonazole	15	3	6	73 (11)	10 (-22 to 43)	0.85 (0.52 to 1.30)
Roberts (1985)^w47	Miconazole	16	3	6	63 (10)	10 (-22 to 43)	0.85 (0.52 to 1.30)
Thomas (1986)^w28	Bifonazole	15	3	3	87 (13)	20 (-15 to 55)	0.76 (0.46 to 1.20)
Thomas (1986)^w28	Sulconazole	9	3	3	67 (6)	20 (-15 to 55)	0.76 (0.46 to 1.20)
Woscoff (1986)^w43	Sulconazole	21	3	5	95 (20)	25 (3 to 47)	0.73 (0.53 to 0.99)
Woscoff (1986)^w43	Miconazole	20	3	5	70 (14)	25 (3 to 47)	0.73 (0.53 to 0.99)
Greer (1987)^w46	Ketoconazole	30	4	8	77 (23)	3 (-18 to 25)	0.95 (0.71 to 1.20)
Greer (1987)^w46	Ketoconazole	30	4	8	73 (22)	3 (-18 to 25)	0.95 (0.71 to 1.20)
Smith II (1988)^w124	Tioconazole	34	6	10	94 (32)	10 (-5 to 26)	0.88 (0.73 to 1.06)
Smith II (1988)^w124	Miconazole	30	6	10	83 (25)	10 (-5 to 26)	0.88 (0.73 to 1.06)
Smith III (1988)^w124	Tioconazole	16	6	10	81 (13)	6 (-25 to 37)	0.92 (0.61 to 1.38)
Smith III (1988)^w124	Miconazole	12	6	10	75 (9)	6 (-25 to 37)	0.92 (0.61 to 1.38)
Kuhlwein (1990)^w35	Croconazole	19	3	5	100 (19)	0 (-17 to 19)	1.0 (0.79 to 1.23)
Kuhlwein (1990)^w35	Bifonazole	17	3	5	100 (17)	0 (-17 to 19)	1.0 (0.79 to 1.23)
Friederich (1992)^w48	Bifonazole: continuous treatment	38	3	6	97 (37)	8 (-3 to 20)	0.91 (0.79 to 1.04)
Friederich (1992)^w48	Bifonazole: intermittent treatment	35	3	6	89 (31)	8 (-3 to 20)	0.91 (0.79 to 1.04)
Tsuboi (1996)^w45	Neticonazole and dressing	44	4	4	52 (23)	-23 (-3 to -41)	1.43 (1.06 to 2.03)
Tsuboi (1996)^w45	Neticonazole	52	4	4	75 (39)	-23 (-3 to -41)	1.43 (1.06 to 2.03)
Other agents in fungal infections of skin
Kligman II (1985)^w2	Ciclopiroxolamine	33	4	6	88 (29)	9 (-8 to 26)	0.89 (0.72 to 1.10)
Kligman II (1985)^w2	Clotrimazole	37	4	6	78 (29)
Carter (1972)^w30	Haloprogen	52	4	5	79 (41)	38 (11 to 60)	0.52 (0.27 to 0.84)
Carter (1972)^w30	Tolnaftate	17	4	5	41 (7)	38 (11 to 60)	0.52 (0.27 to 0.84)
Thomas (1976)^w44	Clotrimazole	14	4	8	86 (12)	36 (-4 to 69)	0.58 (0.25 to 1.04)
Thomas (1976)^w44	Tolnaftate	8	4	8	50 (4)	36 (-4 to 69)	0.58 (0.25 to 1.04)
Holti (1970)^w41	Variotin	4	8	24	75 (3)	8 (-48 to 65)	0.75 (0.32 to 1.74)
Holti (1970)^w41	Whitfield's ointment	6	8	24	67 (4)	8 (-48 to 65)	0.75 (0.32 to 1.74)
Fungal infections of nails
Mensing (1992)^w108	Amorolfine 5% in ethanol	17	4	6	94 (16)	12 (-13 to 37)	0.88 (0.62 to 1.17)
Mensing (1992)^w108	Amorolfine 5% in methylene chloride	17	4	6	82 (14)	12 (-13 to 37)	0.88 (0.62 to 1.17)
Buck (1994)^w107	Clotrimazole	53	26	26	8 (4)	-3 (-15 to 8)	1.45 (0.48 to 4.46)
Buck (1994)^w107	Tea tree oil	64	26	26	11 (7)	-3 (-15 to 8)	1.45 (0.48 to 4.46)

Table D Comparative trials of more than two active topical treatments for fungal skin infections of foot

Trial	Interventions	Sample size	Treatment (weeks)	Follow up (weeks)	% Cure rate (No cured)
Comparison between allylamines and azoles
Smith (1990)^w50	Naftifine twice daily	36	4	6	81 (29)
	Naftifine once daily	65	4	6	66 (43)
	Clotrimazole twice daily	55	4	6	58 (32)
Bergstresser (1993)^w53	Terbinafine	42	4	12	86 (36)
	Terbinafine	38	1	12	76 (29)
	Clotrimazole	43	4	12	70 (30)
	Clotrimazole	37	1	12	35 (13)
Ablon (1996)^w49	Naftifine	29	2	10	75 (22)
	Terbinafine	31	2	10	81 (25)
	Oxiconazole	28	2	10	27 (8)
Comparison between two or more azoles
Ellis (1989)^w59	Oxiconazole nitrate and hydrocortisone	54	4	6	80 (43)
	Oxiconazole nitrate	56	4	6	75 (42)
	Placebo	44	4	6	34 (15)
Elewski (1996)^w55	Oxiconazole nitrate and fluticasone propionate	103	4	6	82 (84)
	Oxiconazole nitrate	98	4	6	65 (64)
	Placebo	96	4	6	31 (30)
Korting (1997)^w51	Econazole gel	159	2	4	79 (34)
	Econazole cream	154	2	4	73 (42)
	Clotrimazole	152	2	4	70 (45)
Comparison between two or more allylamines
Zaug et al 1992^w52	Amorolfine 0.5%	111	4	6	88 (98)
	Amorolfine 0.25%	103	4	6	86 (89)
	Amorolfine 0.125%	123	4	6	87 (107)
Evans (1994)^w54	Terbinafine	12	7 days	12	92 (11)
	Terbinafine	17	5 days	12	88 (15)
	Terbinafine	18	3 days	12	67 (12)
	Terbinafine	18	1 day	12	94 (17)
Other agents
Smith (1977)^w60	Zinc undecenoate	27	6	6	59 (16)
	Old undecenoate	30	6	6	47 (14)
	Placebo	23	6	6	4 (1)
	No treatment	22	6	6	9 (2)
Tschen (1979)^w57	Undecenoic acid	27	4	8	81 (22)
	Tolnaftate	21	4	8	67 (14)
	Placebo	12	4	8	67 (8)
Fuerst (1980)^w56	Undecenoic acid	16	4	6	69 (11)
	Tolnaftate	24	4	6	67 (16)
	Placebo	24	4	6	25 (6)
Tong (1992)^w58	Tolnaftate	33	4	5	85 (28)
	Tea tree oil	37	4	5	30 (11)
	Placebo	34	4	5	21 (7)