NCT00342628

Brief Summary

The purpose of this study is to evaluate the safety, immunogenicity, and compatibility of our Vi-rEPA conjugate administered to infants with their routine vaccinations. We propose to recruit 300 full term healthy newborns in Vietnam and randomly divide them to receive Vi-rEPA plus DTP, Hib-TT (not yet used in Vietnam) plus DTP, or DTP alone. Consent is obtained following interviews of mothers during prenatal visits, or after delivery. All vaccines will be administered at 2, 4, and 6 months. A booster of Vi-rEPA or Hib-TT conjugate will be administered at 12 months of age and reactions monitored at 6, 24 and 48 hours after each injection. Maternal and cord blood samples are collected during labor and at delivery. Blood will be taken at 7, and 12 months of age from all study infants and at 13 months from infants injected with Vi-rEPA or with Hib-TT at 12 months. The blood samples will be assayed for Vi, Hib, diphtheria, tetanus and pertussis antibodies. The levels of serum IgG anti-Vi elicited by Vi-rEPA administered to infants by the above schedule will be compared to those elicited by this vaccine in 2 to 5 year-olds in the efficacy trial conducted in Dong Thap Province, Vietnam.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
301

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2006

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 19, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 21, 2006

Completed
10 days until next milestone

Study Start

First participant enrolled

July 1, 2006

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2008

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2011

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

June 27, 2012

Completed
Last Updated

June 27, 2012

Status Verified

May 1, 2012

Enrollment Period

1.8 years

First QC Date

June 19, 2006

Results QC Date

March 30, 2012

Last Update Submit

May 22, 2012

Conditions

Typhoid Fever

Keywords

AntibodyReactionsVaccineConjugate VaccineTyphoid FeverTrialSafetyImmunogenicityComparabilityDTP

Outcome Measures

Primary Outcomes (1)

  • Number of Infants With Adverse Reactions After Vaccination

    Number of infants with Fever\>=38.0 C, Induration\>=2.5cm at DTP site, Induration\>=2.5cm,Vi-rEPA/Hib-TT site, Erythema\>=2.5cm, at DTP site, Erythema\>=2.5cm, Vi-rEPA/Hib-TT site, Inconsolable crying\<4hr, Inconsolable crying\>=4hr per injection with Vi conjugate vaccine given in conjunction with DTP in infants.

    at 2, 4, 6 and 12 months

Secondary Outcomes (3)

  • IgG Anti-Vi Levels

    cord sera, infants' sera at 7, 12 and 13 months

  • Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin

    Cord sera, and infants' sera at 7, 12 and 13 months of age

  • Antibody Responses to Hib CP

    Cord sera and infant sera at 7, 12, and 13 months

Study Arms (3)

Vi-rEPA plus DTP

EXPERIMENTAL

Vi-rEPA and DTP at 2, 4, 6 months, and Vi-rEPA at 12 months

Biological: Vi-rEPA conjugate vaccine for typhoid feverBiological: DTP

Hib-TT plus DTP

ACTIVE COMPARATOR

Hib-TT and DTP at 2,4 and 6 months, Hib-TT at 12 months

Biological: Hib-TTBiological: DTP

EPI

ACTIVE COMPARATOR

DTP at 2,4 and 6 months

Biological: DTP

Interventions

Vi-rEPA conjugate vaccine for typhoid feverBIOLOGICAL

Vi-rEPA contains a 25 ug/dose of Vi (Sanofi-Pasteur Lot 130) and rEPA in 0.2 N NaCl, 10 mM phosphate PH 7.2 and 0.01% thimerosal.

Also known as: Vi conjugate
Vi-rEPA plus DTP
Hib-TTBIOLOGICAL

Hib-TT is Hemophilus influenzae type b-tetanus toxoid conjugate vaccine (ActHib, NDC#49281-545-05 Sanofi-Pasteur, France) in single-dose vials containing 10 ugof Hib CP conjugated to 24 ug of tetanus toxoid

Also known as: Hib conjugate
Hib-TT plus DTP
DTPBIOLOGICAL

DTP, diphtheria, tetanus toxoid and pertussis vaccine were from the Ministry of Health, Vietnam for routine infant immunization

Also known as: EPI vaccine
EPIHib-TT plus DTPVi-rEPA plus DTP

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy full-term newborns.
  • Birth weights of \>=2500 grams.

You may not qualify if:

  • Newborns without maternal and cord blood samples
  • Newborns born to mothers with serious medical problems.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Thanh Thuy District Health Center

Việt Trì, Phu Tho, Vietnam

Location

Related Publications (13)

  • Acharya IL, Lowe CU, Thapa R, Gurubacharya VL, Shrestha MB, Cadoz M, Schulz D, Armand J, Bryla DA, Trollfors B, et al. Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report. N Engl J Med. 1987 Oct 29;317(18):1101-4. doi: 10.1056/NEJM198710293171801.

    PMID: 3657877BACKGROUND

  • Crump JA, Mintz ED. Global trends in typhoid and paratyphoid Fever. Clin Infect Dis. 2010 Jan 15;50(2):241-6. doi: 10.1086/649541.

    PMID: 20014951BACKGROUND

  • Gilman RH, Terminel M, Levine MM, Hernandez-Mendoza P, Hornick RB. Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet. 1975 May 31;1(7918):1211-3. doi: 10.1016/s0140-6736(75)92194-7.

    PMID: 48834BACKGROUND

  • Klugman KP, Gilbertson IT, Koornhof HJ, Robbins JB, Schneerson R, Schulz D, Cadoz M, Armand J. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet. 1987 Nov 21;2(8569):1165-9. doi: 10.1016/s0140-6736(87)91316-x.

    PMID: 2890805BACKGROUND

  • Kossaczka Z, Lin FY, Ho VA, Thuy NT, Van Bay P, Thanh TC, Khiem HB, Trach DD, Karpas A, Hunt S, Bryla DA, Schneerson R, Robbins JB, Szu SC. Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam. Infect Immun. 1999 Nov;67(11):5806-10. doi: 10.1128/IAI.67.11.5806-5810.1999.

    PMID: 10531232BACKGROUND

  • Mai NL, Phan VB, Vo AH, Tran CT, Lin FY, Bryla DA, Chu C, Schiloach J, Robbins JB, Schneerson R, Szu SC. Persistent efficacy of Vi conjugate vaccine against typhoid fever in young children. N Engl J Med. 2003 Oct 2;349(14):1390-1. doi: 10.1056/NEJM200310023491423. No abstract available.

    PMID: 14523155BACKGROUND

  • Levine MM, Ferreccio C, Abrego P, Martin OS, Ortiz E, Cryz S. Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine. 1999 Oct 1;17 Suppl 2:S22-7. doi: 10.1016/s0264-410x(99)00231-5.

    PMID: 10506405BACKGROUND

  • Lin FY, Vo AH, Phan VB, Nguyen TT, Bryla D, Tran CT, Ha BK, Dang DT, Robbins JB. The epidemiology of typhoid fever in the Dong Thap Province, Mekong Delta region of Vietnam. Am J Trop Med Hyg. 2000 May;62(5):644-8. doi: 10.4269/ajtmh.2000.62.644.

    PMID: 11289678BACKGROUND

  • Lin FY, Ho VA, Khiem HB, Trach DD, Bay PV, Thanh TC, Kossaczka Z, Bryla DA, Shiloach J, Robbins JB, Schneerson R, Szu SC. The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. N Engl J Med. 2001 Apr 26;344(17):1263-9. doi: 10.1056/NEJM200104263441701.

    PMID: 11320385BACKGROUND

  • Ochiai RL, Acosta CJ, Danovaro-Holliday MC, Baiqing D, Bhattacharya SK, Agtini MD, Bhutta ZA, Canh DG, Ali M, Shin S, Wain J, Page AL, Albert MJ, Farrar J, Abu-Elyazeed R, Pang T, Galindo CM, von Seidlein L, Clemens JD; Domi Typhoid Study Group. A study of typhoid fever in five Asian countries: disease burden and implications for controls. Bull World Health Organ. 2008 Apr;86(4):260-8. doi: 10.2471/blt.06.039818.

    PMID: 18438514BACKGROUND

  • Sinha A, Sazawal S, Kumar R, Sood S, Reddaiah VP, Singh B, Rao M, Naficy A, Clemens JD, Bhan MK. Typhoid fever in children aged less than 5 years. Lancet. 1999 Aug 28;354(9180):734-7. doi: 10.1016/S0140-6736(98)09001-1.

    PMID: 10475185BACKGROUND

  • Szu SC, Stone AL, Robbins JD, Schneerson R, Robbins JB. Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. Preparation, characterization, and immunogenicity in laboratory animals. J Exp Med. 1987 Nov 1;166(5):1510-24. doi: 10.1084/jem.166.5.1510.

    PMID: 3681191BACKGROUND

  • Taylor DN, Levine MM, Kuppens L, Ivanoff B. Why are typhoid vaccines not recommended for epidemic typhoid fever? J Infect Dis. 1999 Dec;180(6):2089-90. doi: 10.1086/315159. No abstract available.

    PMID: 10558978BACKGROUND

MeSH Terms

Conditions

Typhoid Fever

Interventions

Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate

Condition Hierarchy (Ancestors)

Salmonella InfectionsEnterobacteriaceae InfectionsGram-Negative Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Results Point of Contact

Title
Feng-Ying (Kimi) Lin, MD, MPH
Organization
PDMI, NICHD, NIH
link@mail.nih.gov
301-496-0295

Study Officials

  • Feng-Ying (Kimi) Lin, MD, MPH

    PDMI, NICHD, NIH

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 19, 2006

First Posted

June 21, 2006

Study Start

July 1, 2006

Primary Completion

April 1, 2008

Study Completion

January 1, 2011

Last Updated

June 27, 2012

Results First Posted

June 27, 2012

Record last verified: 2012-05

Locations

VN(1)