A randomized, observer-blind, controlled phase III clinical trial assessing safety and immunological non-inferiority of Vi-diphtheria toxoid versus Vi-tetanus toxoid typhoid conjugate vaccine in healthy volunteers in eastern Nepal

Figures & data

Figure 1. CONSORT flow diagram showing trial profile.

Table 1. Demographic distribution of the study participants (n = 400).

	Vi-DT Group	Lot 1	Lot 2	Lot 3	Vi-TT Group	Total
Characteristics	N = 300	N = 100	N = 100	N = 100	N = 100	N = 400	p-value
Male (%)	155 (51.67)	53(53.00)	47(47.00)	55(55.00)	52 (52.00)	207(51.75)	.9539*
Female (%)	145 (48.33)	47(47.00)	53(53.00)	45(45.00)	48(48.00)	193(48.25)
Mean (SD)	15.80 (12.56)	15.71 (12.14)	15.72 (12.59)	15.97 (13.05)	15.12(12.28)	15.63 (12.48)	.6378^#
Median (min, max)	15.05 (0.51, 44.69)	14.62 (0.51, 43.85)	15.61 (0.53, 44.59)	15.02 (0.59, 44.69)	13.14 (0.61, 41.01)	14.58 (0.51, 44.69)

*Chi square test; ^#Two sample t test; Vi-DT = Vi-Diphtheria toxoid; Vi-TT = Vi-Tetanus toxoid.

Table 2. Anti-Vi IgG seroconversion rates in Vi-DT vaccine vs Vi-TT vaccine at 4 weeks postvaccination: Immunogenicity set.

4 Weeks Postvaccination	Vi-DT Group		Vi-TT Group		Vi-DT - Vi-TT	p-value^‡
	n/N	Seroconversion rate (97.5% CI)	n/N	Seroconversion rate (97.5% CI)	Difference (97.5% CI)^†
All Ages	298/298	100.00 (98.34, 100.00)	98/99	98.99 (93.39, 99.85)	1.01 (−3.07, 5.09)	.7857
Age Strata1 (6months- <2years)	78/78	100.00 (95.31, 100.00)	26/26	100.00 (87.13, 100.00)	0.00 (0.00, 0.00)	NA
Age Strata2 (2 - <18 years)	107/107	100.00 (96.53, 100.00)	36/36	100.00 (90.36, 100.00)	0.00 (0.00, 0.00)	NA
Age Strata3 (18 - <45 years)	113/113	100.00 (96.71, 100.00)	36/37	97.30 (86.18, 99.52)	2.70 (−3.51, 8.92)	.2467

^†Generalized linear model for binomial distribution; ^‡Generalized linear model for binomial distribution and Fisher’s exact test for age strata 3 p-value; Vi-DT= Vi-Diphtheria toxoid; Vi-TT = Vi-Tetanus toxoid; CI = Confidence Interval.

Table 3. Adverse events profile of participants after vaccination with Vi-DT vs Vi-TT vaccine.

	Vi-DT Group (N = 300)			Vi-TT Group (N = 100)			p value
	Overall	Local AE, n/N** (%)	Systemic AE n/N** (%)	Overall	Local AE n/N** (%)	Systemic AE n/N** (%)
Immediate reactions within 30 minutes postvaccination
All ages	11/300 (3.67%)	10 (3.33%)	1 (0.33%)	3/100 (3.00%)	3 (3.00%)	0 (0.00%)	1.00^#
Age strata 1 (6months- <2years)	4/78 (5.13%)	4 (5.13%)	0 (0.00%)	1/26 (3.85%)	1 (3.85%)	0 (0.00%)	1.00^#
Age strata 2 (2 - <18 years)	2/108 (1.85%)	1 (0.93%)	1 (0.93%)	2/36 (5.56%)	2 (5.56%)	0 (0.00%)	.26^#
Age strata 3 (18 - <45 years)	5/114 (4.39%)	5 (4.39%)	0 (0.00%)	0/38 (0.00%)	0 (0.00%)	0 (0.00%)	.33^#
Solicited adverse events within 7 days after vaccination (related to vaccine)
All ages	101/300 (33.67%)	83 (27.67%)	41 (13.67%)	44/100 (44.00%)	37 (37.00%)	14 (14.00%)	.07*
Age strata 1 (6months- <2years)	27/78 (34.62%)	18 (23.08%)	14 (17.95%)	12/26 (46.15%)	7 (26.92%)	7 (26.92%)	.29*
Age strata 2 (2 - <18 years)	38/108 (35.19%)	34 (31.48%)	10 (9.26%)	19/36 (52.78%)	17 (47.22%)	4 (11.11%)	.06*
Age strata 3 (18 - <45 years)	36/114 (31.58%)	31 (27.19%)	17 (14.91%)	13/38 (34.21%)	13 (34.21%)	3 (7.89%)	.84*
Unsolicited adverse events within 4 weeks after vaccination
All ages	63/300 (21.00%)			18/100 (18.00%)			.51*
Age strata 1 (6months- <2years)	35/78 (44.87%)			13/26 (50.00%)			.64*
Age strata 2 (2 - <18 years)	14/108 (12.96%)			3/36 (8.33%)			.56*
Age strata 3 (18 - <45 years)	14/114 (12.28%)			2/38 (5.26%)			.36*
Serious adverse events during entire study period
All ages	1/300 (0.33%)			2/100 (2.00%)			.15^#
Age strata 1 (6months- <2years)	0 (0.00%)			0 (0.00%)			NA
Age strata 2 (2 - <18 years)	0 (0.00%)			0 (0.00%)			NA
Age strata 3 (18 - <45 years)	1/114 (0.88%)			2/38 (5.26%)			.15^#
Respiratory, thoracic and mediastinal disorders Tubercular pleural effusion	0 (0.00%) 0 (0.00%)			1 (1.00%) 1 (1.00%)			.25^#
Surgical and medical procedures Medical termination of pregnancy	1 (0.33%) 1 (0.33%)			1 (1.00%) 1 (1.00%)			.43^#

*Chi-square test; ^#Fisher’s exact test; n = number of participants reporting the adverse event; N = total number of participants; AE = Adverse Events; Vi-DT = Vi-Diphtheria toxoid; Vi-TT = Vi-Tetanus toxoid.

Table

Week 4 Postvaccination	Vi-DT Group (Pooled Groups A+B+C)		Vi-TT Group		Vi-DT – Vi-TT	p-value^‡
	n/N	Seroconversion rate (97.5% CI)	n/N	Seroconversion rate (97.5% CI)	Difference (97.5% CI)^†
All Ages	291/291	100.00 (98.30, 100.00)	96/97	98.97 (93.27, 99.85)	1.03 (−3.10, 5.17)	.7851
Age Strata1	72/72	100.00 (94.93, 100.00)	24/24	100.00 (86.20, 100.00)	0.00 (0.00, 0.00)	NA
Age Strata2	107/107	100.00 (96.53, 100.00)	36/36	100.00 (90.36, 100.00)	0.00 (0.00, 0.00)	NA
Age Strata3	112/112	100.00 (96.68, 100.00)	36/37	97.30 (86.18, 99.52)	2.70 (−3.54, 8.94)	.2483

^†Generalized linear model for binomial distribution with group and strata as covariates; ^‡Generalized linear model for binomial distribution with group and strata as covariates for p-value for all ages; Fisher’s exact test for p-value for each age strata; Vi-DT = Vi-Diphtheria toxoid; Vi-TT = Vi-Tetanus toxoid; CI = Confidence Interval.

Table

Week 24 Post Vaccination	Vi-DT Group (Pooled Groups A+B+C)		Vi-TT Group		p-value^‡
	n/N	Seroconversion rate (95% CI)	n/N	Seroconversion rate (95% CI)
All Ages	274/277	98.92 (96.86, 99.63)	85/87	97.70 (92.00, 99.37)	.8301
Age Strata1	69/70	98.57 (92.34, 99.75)	20/20	100.00 (83.89, 100.00)	1.0000
Age Strata2	102/102	100.00 (96.37, 100.00)	34/34	100.00 (89.85, 100.00)	NA
Age Strata3	103/105	98.10 (93.32, 99.48)	31/33	93.94 (80.39, 98.32)	.2418

^‡Generalized linear model for binomial distribution with group and strata as covariates for p-value for all ages; Fisher’s exact test for p-value for each age strata; Vi-DT = Vi-Diphtheria toxoid; Vi-TT = Vi-Tetanus toxoid; CI = Confidence Interval.