Helicobacter pylori Eradication and Gastric Preneoplastic Conditions: A Randomized, Double-Blind, Placebo-Controlled Trial

Catherine Ley; Alejandro Mohar; Jeannette Guarner; Roberto Herrera-Goepfert; Luz Sanchez Figueroa; David Halperin; Iain Johnstone; Julie Parsonnet

doi:10.1158/1055-9965.EPI-03-0124

DOI: 10.1158/1055-9965.EPI-03-0124 Published January 2004

Article Figures & Data

Tables

Table 1

Frequency of demographic, serological, and medical characteristics in enrolled subjects who completed the study (n = 248)^a

No serious adverse effects of treatment were reported. Minor side effects were common (40.6% overall), but only dysgeusia was more prevalent among treatment compared with placebo subjects (78% vs. 30%; P ≤ 0.001). Compliance with treatment was very high (93% overall).

	Placebo (n = 126)	Treatment (n = 122)	P^b
Age (mean ± SD), years	52.0 ± 9.76	51.0 ± 9.22	0.40
Female gender, n (%)	79 (62.7)	78 (63.9)	0.84
CagA antibody, n (%)
Positive	123 (97.6)	116 (95.1)	0.33
Borderline	3 (2.4)	6 (4.9)
Diabetic
Yes	10 (7.9)	6 (4.9)	0.72
Unknown	1 (0.8)	1 (0.8)
Smoking history
None	75 (59.5)	67 (54.9)	0.80
Former	32 (25.4)	37 (30.3)
Occasional	14 (11.1)	12 (9.8)
Regular	5 (4.0)	6 (4.9)
History of vitamin use,^c n (%)
None	28 (22.2)	25 (20.5)	0.88
Former	27 (21.4)	24 (19.7)
Occasional	67 (53.2)	67 (54.9)
Regular	4 (3.2)	6 (4.9)
History of alcohol use, n (%)
None	17 (13.5)	19 (15.6)	0.59
Former	22 (17.5)	21 (17.2)
Occasional	83 (65.9)	74 (60.7)
Regular	4 (3.2)	8 (6.6)
Known family history of gastric cancer, n (%)	12 (9.5)	7 (5.7)	0.43

a Sixty-eight enrolled subjects who withdrew were not different from those who completed the study.
b t Test, χ² test, or Fisher’s exact test, as appropriate.
c Dietary components other than vitamin use and alcohol consumption were not assessed.

Table 2

Baseline histologic characteristics and stomach index score of enrolled subjects who completed the study by trial arm^a

Characteristic	Placebo (n = 126)	Treatment (n = 122)	P
Gastritis, n (%)
None	0	1 (0.8)	0.03
Chronic	14 (11.1)	4 (3.3)
Acute	112 (88.9)	117 (95.9)
Atrophy, n (%)
None	47 (37.3)	56 (45.9)	0.22
Mild	39 (31.0)	28 (23.0)
Moderate	36 (28.6)	30 (24.6)
Severe	4 (3.2)	8 (6.6)
IM,^c n (%)
None	60 (48.0)	61 (50.0)	0.08
Mild	18 (14.4)	26 (21.3)
Moderate	17 (13.6)	6 (4.9)
Severe	30 (24.0)	29 (23.8)
Dysplasia, n (%)
None	106 (84.1)	112 (91.8)	0.14
Mild	18 (14.3)	8 (6.6)
Moderate	2 (1.6)	2 (1.6)
Severe	0	0
Worst biopsy diagnosis,^d n (%)
Normal	0	1 (0.8)	0.83
Gastritis	51 (40.5)	46 (37.7)
Atrophy^e	10 (7.9)	14 (11.5)
IM	63 (50.0)	59 (48.4)
Dysplasia^e	2 (1.6)	2 (1.6)
Stomach index score,^f n (%)
Median	0.50	0.50	0.93
25%–75%	0–2.0	0–1.9
Range	0–13.7	0–15.3

a Enrolled subjects who withdrew were not different at baseline from those who completed the study.
b χ² test, Fisher’s exact test or median test, as appropriate.
c IM, intestinal metaplasia.
d Normal < chronic/active gastritis < moderate/severe atrophy < mild/moderate/severe IM < moderate dysplasia.
e To prevent misclassification, worst diagnoses of mild atrophy were grouped with gastritis because all of these subjects had underlying inflammation. Worst diagnoses of mild dysplasia were grouped with the next worst condition for each subject.
f Average score across both pathologists.

Table 3

Intention-to-treat analysis: Change over time in both worst biopsy diagnosis and stomach index score among all enrolled subjects by trial arm (n = 126 placebo, 122 treatment)^a

	Baseline to 6 weeks					6 weeks to 1 year
		Placebo	Treatment	P^b	Placebo	Treatment	P	Placebo	Treatment	P
Worst biopsy diagnosis,^c n (%)
Worsening	17 (13.7)	14 (11.7)	0.85	13 (10.5)	10 (8.3)	0.74	11 (8.7)	11 (9.0)	0.98
No change	84 (67.7)	85 (70.8)		87 (70.2)	83 (69.2)		84 (66.7)	80 (65.6)
Improvement	23 (18.6)	21 (17.5)		24 (19.4)	27 (22.5)		31 (24.6)	31 (25.4)
Change in score (mean ± SD)
Average^d	−0.12 ± 2.51	0.27 ± 2.47	0.22	−0.14 ± 1.92	−0.77 ± 2.37	0.03	−0.23 ± 2.25	−0.5 ± 2.43	0.36
Pathologist 1	−0.13 ± 2.00	−0.18 ± 2.42	0.86	0.10 ± 1.76	−0.50 ± 1.51	0.005	−0.01 ± 2.30	−0.69 ± 2.32	0.02
Pathologist 2	−0.11 ± 4.30	0.73 ± 3.96	0.12	−0.38 ± 2.58	−1.0 ± 3.98	0.13	−0.45 ± 3.46	−0.31 ± 3.28	0.74

a Four subjects (two placebo, two treatment) were missing their second endoscopy.
b χ² or t test, as appropriate.
c Normal < chronic or active gastritis < moderate or severe atrophy < mild, moderate, or severe intestinal metaplasia < moderate dysplasia.
d Mean of both pathologists’ difference in score. Variances were unequal for all time intervals.

Table 4

Per-eradication-protocol analysis: Change over time in both worst biopsy diagnosis and stomach index score among enrolled subjects who met eradication protocol by trial arm (n = 104 placebo, 75 treatment)^a

	Baseline to 6 weeks					6 weeks to 1 year
		Placebo	Treatment	P^b	Placebo	Treatment	P	Placebo	Treatment	P
Worst biopsy diagnosis,^c n (%)
Worsening	15 (14.4)	9 (12.0)	0.76	12 (11.5)	6 (8.0)	0.47	11 (10.6)	9 (12.0)	0.96
No change	68 (65.4)	53 (70.7)		75 (72.1)	52 (69.3)		68 (65.4)	48 (64.0)
Improvement	21 (20.2)	13 (17.3)		17 (16.4)	17 (22.7)		25 (24.0)	18 (24.0)
Change in score (mean ± SD)
Average^d	−0.20 ± 2.62	0.27 ± 2.37	0.22	−0.07 ± 1.99	−0.84 ± 2.21	0.02	−0.27 ± 2.42	−0.57 ± 2.15	0.39
Pathologist 1	−0.18 ± 2.13	−0.11 ± 2.42	0.85	0.15 ± 1.88	−0.52 ± 1.73	0.02	−0.03 ± 2.44	−0.63 ± 2.25	0.10
Pathologist 2	−0.22 ± 4.49	0.66 ± 4.04	0.18	−0.20 ± 2.55	−1.17 ± 3.42	0.06	−0.50 ± 3.77	−0.51 ± 3.02	0.99

a Baseline H. pylori positive by histology and either (a) H. pylori positive at 6 weeks and 1 year if in the placebo group or (b) H. pylori negative at 6 weeks and 1 year if in the treatment group.
b χ² test or t test, as appropriate.
c Normal < chronic or active gastritis < moderate or severe atrophy < mild, moderate, or severe intestinal metaplasia < moderate dysplasia.
d Mean of both pathologists’ difference in score. Variances were unequal for all time intervals.

Table 5

Stomach index scores based on seven biopsies for a series of hypothetical profiles^a

Biopsies with preneoplastic findings	Stomach index score
Unaffected	0.00
One mild IM^b
One moderate atrophy
One moderate IM	0.50
One severe atrophy
One severe IM
Two mild IM	1.15
Two moderate atrophy	1.41
Two moderate IM	1.55
One moderate atrophy/one mild IM	1.82
One mild IM/one moderate IM	1.91
Six mild IM	2.00
Two severe atrophy	2.00
Four moderate atrophy	2.00
Two severe IM	2.00
Five moderate IM	2.45
Three severe IM	2.45
One moderate atrophy/two moderate IM	2.55
Seven moderate atrophy	2.65
Four severe atrophy	2.83
One mild IM/one moderate IM/one severe IM	3.33
Two severe atrophy/two moderate IM	3.55
Three moderate atrophy/three moderate IM	3.63
Seven severe IM	3.74
Seven severe atrophy	3.74
Seven severe atrophy/seven severe IM	7.48
One moderate dysplasia	10.00
Two moderate dysplasia	14.14
Seven severe atrophy/seven severe IM/seven moderate dysplasia	33.94

a If a single biopsy of seven total was affected with moderate or severe atrophy or IM of any degree, then score Y_i = 0.5. Otherwise, Y_i = [(1.00 ∗ (n_{moderate ATROi})^0.5 + 1.4142 ∗ (n_{severe ATRO})^0.5] + 2.70 ∗ [(0.3024 ∗ (n_{mild IMi})^0.5 + 0.4057 ∗ (n_{moderate IMi})^0.5 + 0.5238 ∗ (n_{severe IMi})^0.5] + 10.00 ∗ (1.00 ∗ n_{moderate DYSPi})^0.5], where n is the number of biopsies with each condition.
b IM, intestinal metaplasia.