Zika in Infants and Pregnancy (ZIP)

Zika Virus Disease (Disorder) Clinical Trial

Official title:

International Prospective Observational Cohort Study of Zika in Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02856984
• Other study ID #: GN ZIKA
• Status: Completed
• Start date: June 2016
• Est. completion date: May 5, 2020

Study information

• Verified date: August 2021
• Source: RTI International
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6461
• Est. completion date: May 5, 2020
• Est. primary completion date: May 5, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Disease
• Virus Diseases
• Zika Virus Disease (Disorder)
• Zika Virus Infection

Locations

Country	Name	City	State
Brazil	Departamento de Medicina Tropical da Universidade Federal de Pernambuco-UFPE	Recife	PE
Brazil	Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900 - Monte Alegre	Ribeirão Preto	SP
Brazil	Instituto Fernandes Figueira - FIOCRUZ	Rio de Janeiro	RJ
Brazil	Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS; Rue Waldemar Falcao	Salvador	Bahia
Colombia	Centro Medico Imbanaco	Cali
Guatemala	Fundación para la Alimentación y Nutrición de Centro América y Panamá (INCAP)	Guatemala
Nicaragua	MINSA Central	Managua
Peru	Universidad Peruana	Lima
Puerto Rico	University of Puerto Rico - Recinto de Río Piedras	San Juan
Puerto Rico	University of Puerto Rico Medical Sciences Campus	San Juan

Sponsors (5)

Lead Sponsor	Collaborator
RTI International	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Environmental Health Sciences (NIEHS), Oswaldo Cruz Foundation

Countries where clinical trial is conducted

Brazil,  Colombia,  Guatemala,  Nicaragua,  Peru,  Puerto Rico, 

References & Publications (26)

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. — View Citation

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Berger I. Prenatal microcephaly: can we be more accurate? J Child Neurol. 2009 Jan;24(1):97-100. doi: 10.1177/0883073808321045. — View 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 Baião 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. Epub 2016 Mar 4. — View Citation

CDC Zika Virus; Areas with Zika http://www.cdc.gov/zika/geo/index.html

CDC. Chikungunya virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/chikungunya/hc/clinicalevaluation.html

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.

CDC. Zika virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. http://www.cdc.gov/zika/index.html

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. — View 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. — View Citation

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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. — View Citation

http://www.salud.gov.pr/Estadisticas-Registros-y-Publicaciones/Informes %20Arbovirales/Reporte%20ArboV%20semana%204-2016.pdf

Hutchon DJ. Fetal ultrasound biometry: 1. Head reference values. Br J Obstet Gynaecol. 1999 Aug;106(8):875-6. — View 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

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. — View 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

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, Muñoz 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. — View 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. — View 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. — View 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. — View Citation

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Sarno M, Sacramento GA, Khouri R, do Rosário 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. — View 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. — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of congenital malformations for ZIKV infected participants	To measure the incidence of congenital malformations in fetuses/infants.	Time of birth of infant
Primary	Incidence of congenital malformations for ZIKV infected participants	To measure the incidence of congenital malformations in fetuses/infants.	3 months of age
Primary	Incidence of congenital malformations for ZIKV infected participants	To measure the incidence of congenital malformations in fetuses/infants.	6 months of age
Primary	Incidence of congenital malformations for ZIKV infected participants	To measure the incidence of congenital malformations in fetuses/infants.	12 months of age
Primary	Incidence of adverse fetal outcomes for ZIKV infected participants	To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, central nervous system (CNS) malformations, hydrops, and ocular abnormalities) in fetuses/infants.	Time of birth of infant
Primary	Incidence of adverse fetal outcomes for ZIKV infected participants	To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, central nervous system (CNS) malformations, hydrops, and ocular abnormalities) in fetuses/infants.	3 months of age
Primary	Incidence of adverse fetal outcomes for ZIKV infected participants	To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, central nervous system (CNS) malformations, hydrops, and ocular abnormalities) in fetuses/infants.	6 months of age
Primary	Incidence of adverse fetal outcomes for ZIKV infected participants	To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, central nervous system (CNS) malformations, hydrops, and ocular abnormalities) in fetuses/infants.	12 months of age
Primary	Incidence of congenital malformations for ZIKV symptomatic participants	To measure the incidence of congenital malformations in fetuses/infants.	Time of birth of infant
Primary	Incidence of congenital malformations for ZIKV symptomatic participants	To measure the incidence of congenital malformations in fetuses/infants.	3 months of age
Primary	Incidence of congenital malformations for ZIKV symptomatic participants	To measure the incidence of congenital malformations in fetuses/infants.	6 months of age
Primary	Incidence of congenital malformations for ZIKV symptomatic participants	To measure the incidence of congenital malformations in fetuses/infants.	12 months of age
Primary	Incidence of adverse fetal outcomes for ZIKV symptomatic participants	To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, CNS malformations, hydrops, and ocular abnormalities) in fetuses/infants.	Time of birth of infant
Primary	Incidence of adverse fetal outcomes for ZIKV symptomatic participants	To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, CNS malformations, hydrops, and ocular abnormalities) in fetuses/infants.	3 months of age
Primary	Incidence of adverse fetal outcomes for ZIKV symptomatic participants	To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, CNS malformations, hydrops, and ocular abnormalities) in fetuses/infants.	6 months of age
Primary	Incidence of adverse fetal outcomes for ZIKV symptomatic participants	To measure the incidence of adverse fetal outcomes (including microcephaly, fetal demise, neonatal death, CNS malformations, hydrops, and ocular abnormalities) in fetuses/infants.	12 months of age