Clinical trial NCT02856984: Zika in Infants and Pregnancy (ZIP)
Official title: International Prospective Observational Cohort Study of Zika in Infants
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Zika Virus Disease (Disorder)
Keywords: Pregnancy
Infant
Lead sponsor: RTI International
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: National Institute of Environmental Health Sciences (NIEHS)
name: Oswaldo Cruz Foundation
First posted: 2016-08-05
Enrollment: 6461
Sex: FEMALE
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will recruit up to 10,000 pregnant women up to 17 weeks and 6 days gestation and subjects at any gestational age with acute Zika infection, confirmed by serology or PCR (polymerase chain reaction) test from ZIKV-endemic regions and follow them longitudinally to study the impact of incident ZIKV during pregnancy on maternal, fetal, and newborn outcomes. Researchers will identify cases of incident ZIKV among pregnant women by monitoring for symptoms of Zika-like illness and performing serial laboratory sampling for diagnosis of seroconversion and viral shedding. After delivery, infants born with evidence of ZIKV or born to mothers diagnosed with incident virus infection will be followed in a prospective longitudinal cohort for at least 1 year. In addition, a control group of infants born to mothers without evidence of ZIKV during pregnancy will be followed.

Brief summary: The overall objective of this multisite, multicountry Zika in Infants and Pregnancy (ZIP) study is to assess the strength of the association between Zika virus infection (ZIKV) during pregnancy and adverse maternal/fetal outcomes and the risk of vertical transmission. The study will prospectively enroll a cohort of pregnant women up to 17 weeks and 6 days gestation and subjects at any gestational age with acute Zika infection, confirmed by serology or PCR (polymerase chain reaction) test. The study will follow these women through their pregnancy to identify for clinical evidence of acute ZIKV, while controlling for potential confounders. Outcomes in the women, the developing fetus, and infants will be assessed. All protocol-specified data will be recorded and entered in a central data management system for the purposes of analysis of composite data from the study.

Detailed description: The overall objective of this multisite, multicountry Zika in Infants and Pregnancy (ZIP) study is to assess the strength of the association between Zika virus infection (ZIKV) during pregnancy and adverse maternal/fetal outcomes and the risk of vertical transmission. The study will prospectively enroll a cohort of pregnant women up to 17 weeks and 6 days gestation and subjects at any gestational age with acute Zika infection, confirmed by serology or PCR (polymerase chain reaction) test. The study will follow these women through their pregnancy to identify for clinical evidence of acute ZIKV, while controlling for potential confounders. Outcomes in the women, the developing fetus, and infants will be assessed. All protocol-specified data will be recorded and entered in a central data management system for the purposes of analysis of composite data from the study.

The study will recruit up to10,000 pregnant women in their first trimester from ZIKV-endemic regions and follow them longitudinally to study the impact of incident ZIKV during pregnancy on maternal, fetal, and newborn outcomes. Researchers will identify cases of incident ZIKV among pregnant women by monitoring for symptoms of Zika-like illness and performing serial laboratory sampling for diagnosis of seroconversion and viral shedding. After delivery, infants born with evidence of ZIKV or born to mothers diagnosed with incident virus infection will be followed in a prospective longitudinal cohort for at least 1 year. In addition, a control group of infants born to mothers without evidence of ZIKV during pregnancy will be followed.

Eligibility criteria: Inclusion Criteria:

* Informed consent
* Age \>15 years
* Assent and consent as required per local country regulations
* Confirmation of pregnancy by beta human chorionic gonadotropin (hCG) measurement in blood/urine or ultrasound confirmation of pregnancy with fetal heart tones present
* Pregnant women up to 17 weeks and 6 days gestation and subjects at any gestational age with acute Zika infection, confirmed by serology or PCR (polymerase chain reaction) test.

Exclusion Criteria: Pregnant Women

* Women who cannot adhere to proposed testing schedule
* Pregnant women enrolled in other research including other ZIKV research

Inclusion Criteria (newborn)

* All infants born to women enrolled in the observational cohort are eligible for enrollment

Exclusion Criteria (newborn)

* Mother or custodial parent does not consent to have child participate
* Infants born to mothers that are not part of the ZIP cohort study

Primary outcomes:
measure: Incidence of congenital malformations for ZIKV infected participants
timeFrame: Time of birth of infant
measure: Incidence of congenital malformations for ZIKV infected participants
timeFrame: 3 months of age
measure: Incidence of congenital malformations for ZIKV infected participants
timeFrame: 6 months of age
measure: Incidence of congenital malformations for ZIKV infected participants
timeFrame: 12 months of age
measure: Incidence of adverse fetal outcomes for ZIKV infected participants
timeFrame: Time of birth of infant
measure: Incidence of adverse fetal outcomes for ZIKV infected participants
timeFrame: 3 months of age
measure: Incidence of adverse fetal outcomes for ZIKV infected participants
timeFrame: 6 months of age
measure: Incidence of adverse fetal outcomes for ZIKV infected participants
timeFrame: 12 months of age
measure: Incidence of congenital malformations for ZIKV symptomatic participants
timeFrame: Time of birth of infant
measure: Incidence of congenital malformations for ZIKV symptomatic participants
timeFrame: 3 months of age
measure: Incidence of congenital malformations for ZIKV symptomatic participants
timeFrame: 6 months of age
measure: Incidence of congenital malformations for ZIKV symptomatic participants
timeFrame: 12 months of age
measure: Incidence of adverse fetal outcomes for ZIKV symptomatic participants
timeFrame: Time of birth of infant
measure: Incidence of adverse fetal outcomes for ZIKV symptomatic participants
timeFrame: 3 months of age
measure: Incidence of adverse fetal outcomes for ZIKV symptomatic participants
timeFrame: 6 months of age
measure: Incidence of adverse fetal outcomes for ZIKV symptomatic participants
timeFrame: 12 months of age
Secondary outcomes:
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS; Rue Waldemar Falcao
state: Bahia
city: Recife
country: Brazil
facility: Departamento de Medicina Tropical da Universidade Federal de Pernambuco-UFPE
state: PE
city: Rio de Janeiro
country: Brazil
facility: Instituto Fernandes Figueira - FIOCRUZ
state: RJ
city: Ribeirão Preto
country: Brazil
facility: Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900 - Monte Alegre
state: SP
city: Cali
country: Colombia
facility: Centro Medico Imbanaco
city: Guatemala
country: Guatemala
facility: Fundación para la Alimentación y Nutrición de Centro América y Panamá (INCAP)
city: Managua
country: Nicaragua
facility: MINSA Central
city: Lima
country: Peru
facility: Universidad Peruana
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico Medical Sciences Campus
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico - Recinto de Río Piedras
Study officials:
affiliation: Departamento de Medicina Tropical da Universidade Federal de Pernambuco-UFPE
name: Ricardo Ximenes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama Birmingham School of Medicine
name: William Britt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ribeirão Preto Medical School, University of São Paulo
name: Marisa Mussi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University, Laboratory of Epidemiology and Public Health
name: Albert Ko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS
name: Deolinda Scalabrin
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Fernandes Figueira - FIOCRUZ
name: Marisa Elisabeth Lopes
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundación para la Alimentación y Nutrición de Centro América y Panamá (INCAP)
name: Ana Garces, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Georgia
name: Jose Cordero, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Puerto Rico
name: Carmen Milagros Velez Vega, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard University School of Public Health
name: George Seage, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Puerto Rico
name: Carmen Zorilla, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Californina Berkeley
name: Eva Harris, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: MINSA Central
name: Angel Balmaseda
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Jude Children's Research Hospital
name: Juan F Arias, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RTI International
name: Jill Lebov, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad Peruana Cayetano Heredia
name: Teresa Ochoa Woodell, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: WHO statement on the first meeting of the International Health Regulations (2005) (IHR 2005) Emergency Committee on Zika virus and observed increase in neurological disorders and neonatal malformations; 1 February 2016. Available at http://www.who.int/ mediacentre/news/statements/2016/1st-emergency-committee-zika/en/
citation: Petersen EE, Staples JE, Meaney-Delman D, Fischer M, Ellington SR, Callaghan WM, Jamieson DJ. Interim Guidelines for Pregnant Women During a Zika Virus Outbreak--United States, 2016. MMWR Morb Mortal Wkly Rep. 2016 Jan 22;65(2):30-3. doi: 10.15585/mmwr.mm6502e1.
citation: Powles R, Smith C, Milan S, Treleaven J, Millar J, McElwain T, Gordon-Smith E, Milliken S, Tiley C. Human recombinant GM-CSF in allogeneic bone-marrow transplantation for leukaemia: double-blind, placebo-controlled trial. Lancet. 1990 Dec 8;336(8728):1417-20. doi: 10.1016/0140-6736(90)93111-2.
citation: CDC. Chikungunya virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/chikungunya/hc/clinicalevaluation.html
citation: Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition. Geneva: World Health Organization; 2009. Available from http://www.ncbi.nlm.nih.gov/books/NBK143157/
citation: CDC Zika Virus; Areas with Zika http://www.cdc.gov/zika/geo/index.html
citation: Oliveira Melo AS, Malinger G, Ximenes R, Szejnfeld PO, Alves Sampaio S, Bispo de Filippis AM. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol. 2016 Jan;47(1):6-7. doi: 10.1002/uog.15831. No abstract available.
citation: CDC. West Nile virus: insect repellent use & safety. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/westnile/faq/repellent.html.
citation: CDC. Zika virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/zika/index.html
citation: Oduyebo T, Petersen EE, Rasmussen SA, Mead PS, Meaney-Delman D, Renquist CM, Ellington SR, Fischer M, Staples JE, Powers AM, Villanueva J, Galang RR, Dieke A, Munoz JL, Honein MA, Jamieson DJ. Update: Interim Guidelines for Health Care Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure - United States, 2016. MMWR Morb Mortal Wkly Rep. 2016 Feb 12;65(5):122-7. doi: 10.15585/mmwr.mm6505e2.
citation: Babaliche P, Doshi D. Catching Dengue Early: Clinical Features and Laboratory Markers of Dengue Virus Infection. J Assoc Physicians India. 2015 May;63(5):38-41.
citation: Wahala WM, Silva AM. The human antibody response to dengue virus infection. Viruses. 2011 Dec;3(12):2374-95. doi: 10.3390/v3122374. Epub 2011 Nov 25.
citation: Gibney KB, Edupuganti S, Panella AJ, Kosoy OI, Delorey MJ, Lanciotti RS, Mulligan MJ, Fischer M, Staples JE. Detection of anti-yellow fever virus immunoglobulin m antibodies at 3-4 years following yellow fever vaccination. Am J Trop Med Hyg. 2012 Dec;87(6):1112-5. doi: 10.4269/ajtmh.2012.12-0182. Epub 2012 Oct 29.
citation: Roehrig JT, Nash D, Maldin B, Labowitz A, Martin DA, Lanciotti RS, Campbell GL. Persistence of virus-reactive serum immunoglobulin m antibody in confirmed west nile virus encephalitis cases. Emerg Infect Dis. 2003 Mar;9(3):376-9. doi: 10.3201/eid0903.020531.
citation: http://www.salud.gov.pr/Estadisticas-Registros-y-Publicaciones/Informes %20Arbovirales/Reporte%20ArboV%20semana%204-2016.pdf
citation: Chervenak FA, Jeanty P, Cantraine F, Chitkara U, Venus I, Berkowitz RL, Hobbins JC. The diagnosis of fetal microcephaly. Am J Obstet Gynecol. 1984 Jul 1;149(5):512-7. doi: 10.1016/0002-9378(84)90027-9.
citation: Chervenak FA, Rosenberg J, Brightman RC, Chitkara U, Jeanty P. A prospective study of the accuracy of ultrasound in predicting fetal microcephaly. Obstet Gynecol. 1987 Jun;69(6):908-10.
citation: Kurtz AB, Wapner RJ, Rubin CS, Cole-Beuglet C, Ross RD, Goldberg BB. Ultrasound criteria for in utero diagnosis of microcephaly. J Clin Ultrasound. 1980 Feb;8(1):11-6. doi: 10.1002/jcu.1870080104.
citation: Hutchon DJ. Fetal ultrasound biometry: 1. Head reference values. Br J Obstet Gynaecol. 1999 Aug;106(8):875-6. doi: 10.1111/j.1471-0528.1999.tb08417.x. No abstract available.
citation: Berger I. Prenatal microcephaly: can we be more accurate? J Child Neurol. 2009 Jan;24(1):97-100. doi: 10.1177/0883073808321045.
citation: Julie A Boom; Microcephaly in infants and children: Etiology and evaluation UpToDate http://www.uptodate.com/contents/microcephaly-in-infants-and-children- etiology-and-evaluation?source=machineLearning&search=microcephaly+in +pregnacy&selectedTitle=2~130§ionRank=3&anchor=H55603463#H55603463 Accessed on February 16, 2016
citation: Tolmie JL, McNay M, Stephenson JB, Doyle D, Connor JM. Microcephaly: genetic counselling and antenatal diagnosis after the birth of an affected child. Am J Med Genet. 1987 Jul;27(3):583-94. doi: 10.1002/ajmg.1320270311.
citation: Atkinson B, Hearn P, Afrough B, Lumley S, Carter D, Aarons EJ, Simpson AJ, Brooks TJ, Hewson R. Detection of Zika Virus in Semen. Emerg Infect Dis. 2016 May;22(5):940. doi: 10.3201/eid2205.160107. No abstract available.
citation: Medscape Medical News; FDA Issues Guidance to Protect Blood Supply From Zika Virus http://www.medscape.com/viewarticle/858976? nlid=100283_3901&src=wnl_newsalrt_160216_MSCPEDIT&uac=17333MK&impID=993653&faf=1
citation: Sarno M, Sacramento GA, Khouri R, do Rosario MS, Costa F, Archanjo G, Santos LA, Nery N Jr, Vasilakis N, Ko AI, de Almeida AR. Zika Virus Infection and Stillbirths: A Case of Hydrops Fetalis, Hydranencephaly and Fetal Demise. PLoS Negl Trop Dis. 2016 Feb 25;10(2):e0004517. doi: 10.1371/journal.pntd.0004517. eCollection 2016 Feb.
citation: Brasil P, Pereira JP Jr, Moreira ME, Ribeiro Nogueira RM, Damasceno L, Wakimoto M, Rabello RS, Valderramos SG, Halai UA, Salles TS, Zin AA, Horovitz D, Daltro P, Boechat M, Raja Gabaglia C, Carvalho de Sequeira P, Pilotto JH, Medialdea-Carrera R, Cotrim da Cunha D, Abreu de Carvalho LM, Pone M, Machado Siqueira A, Calvet GA, Rodrigues Baiao AE, Neves ES, Nassar de Carvalho PR, Hasue RH, Marschik PB, Einspieler C, Janzen C, Cherry JD, Bispo de Filippis AM, Nielsen-Saines K. Zika Virus Infection in Pregnant Women in Rio de Janeiro. N Engl J Med. 2016 Dec 15;375(24):2321-2334. doi: 10.1056/NEJMoa1602412. Epub 2016 Mar 4.
citation: Lebov JF, Arias JF, Balmaseda A, Britt W, Cordero JF, Galvao LA, Garces AL, Hambidge KM, Harris E, Ko A, Krebs N, Marques ETA, Martinez AM, McClure E, Miranda-Filho DB, Moreira MEL, Mussi-Pinhata MM, Ochoa TJ, Osorio JE, Scalabrin DMF, Schultz-Cherry S, Seage GR 3rd, Stolka K, Ugarte-Gil CA, Vega CMV, Welton M, Ximenes R, Zorrilla C. International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol. BMC Pregnancy Childbirth. 2019 Aug 7;19(1):282. doi: 10.1186/s12884-019-2430-4.