Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618000266268
Ethics application status
Approved
Date submitted
13/02/2018
Date registered
21/02/2018
Date last updated
21/02/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A comparative study looking at the prevalence of human papilloma virus (HPV) and HPV types in term and preterm labour cases by testing placentae, high vaginal swabs and maternal blood (cfDNA) (HIPPOP trial).
Scientific title
A case control study to determine the prevalence of HPV in preterm labour and preterm prelabour rupture of membranes, the association between HPV and these clinical presentations, and the potential immunological processes underlying preterm labour
Secondary ID [1] 294031 0
None
Universal Trial Number (UTN)
Trial acronym
HIPPOP trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preterm labour (PTL) 306566 0
Premature preterm rupture of membranes (PPROM) 306567 0
Human Papilloma Virus (HPV) 306568 0
Condition category
Condition code
Reproductive Health and Childbirth 305661 305661 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 305662 305662 0 0
Antenatal care
Infection 305663 305663 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Condition investigated is preterm labour (PTL) and premature preterm rupture of membranes (PPROM) and its association with HPV. We are looking at women who go into labour before 37 weeks gestation or experience PPROM before 37 weeks gestation (even if delivery is over 37 weeks gestation). The final mode of delivery does not matter and we do not follow them afterward. The samples required include high vaginal swab, maternal blood test, and placental sample. The blood and swab are collected during labour, while the placental sample is collected soon after birth.
Intervention code [1] 300303 0
Not applicable
Comparator / control treatment
Compared with women who experience term labour, regardless of final mode of delivery. The samples required are the same as for PTL cases and include high vaginal swab, maternal blood test, and placental sample. The blood and swab are collected during labour, while the placental sample is collected soon after birth.
Control group
Active

Outcomes
Primary outcome [1] 304768 0
To determine the prevalence of HPV infection in cases of preterm labour or preterm prelabour rupture of membranes compared with normal term labour. The outcome is assessed by testing three samples: high vaginal swab collective during labour, maternal blood collected during labour, and placenta tissue (sample pf or whole placenta) collected soon after delivery. We are testing for HPV presence (positive or negative) in each sample separately to assess correlation between the three tests, as well as testing for the type of HPV on the swab and the placental tissue.
Timepoint [1] 304768 0
At the time of labour or delivery
Secondary outcome [1] 343091 0
To explore the association between a woman’s cervical smear history (any abnormal smears), smoking, and other potential predictors and the odds of a preterm labour or preterm prelabour rupture of membranes. A women's medical history is collation of information from medical records, self reporting (questionnaire), and national databases for smear and vaccination status.
Timepoint [1] 343091 0
At the time of labour compared with historical information
Secondary outcome [2] 343092 0
To describe prevalence estimates for 30 different types of HPV in cases of threatened preterm labour, preterm labour, PPROM and term labour, to inform future research planning. If one of the tests for a specific case is positive for HPV we will try to test for the type of HPV by using special laboratory equipment. The testing of specific type of HPV is only done for the swab and the placenta sample, not for the blood.
Timepoint [2] 343092 0
At analysis, about 6 month from completion of recruitment
Secondary outcome [3] 343093 0
To explore the immunological process associated with HPV presence at the fetomatenal interface in term and PTL cases. This will be done by assessing the placental sample in the lab with specialised staining and tests.
Timepoint [3] 343093 0
At analysis, about 6 month from recruitment completion

Eligibility
Key inclusion criteria
- Maternal age over 18 years at the time of consent.
- Women in labour or threatened labour at any time during their second and third trimesters.
- Induction of labour at term or post dates for reasons other than concerns for mother or baby, including but not limited to postdates state, social reasons, and previous assisted delivery and/or perineal tear.
- Women presenting with PTL and need to undergo caesarean section due to previous caesarean section.
- Women with previous PTL or PPROM.
- Women with shortened cervical length, with or without progesterone treatment, and those with diagnosis of cervical incompetence.
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Women under 18 years of age at the time of consent.
- Iatrogenic delivery for maternal or fetal concerns, for example emergency caesarean section or induction of labour (IOL) for a baby with restricted growth and abnormal blood supply (=IUGR baby with abnormal dopplers), or maternal pre-eclamplsia.
- Women undergoing elective caesarean section.
- Women with multiple pregnancy, or known uterine anomalies.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Case control
Timing
Prospective
Statistical methods / analysis
With a 2:1 sampling ratio of controls and cases respectively, and estimated HPV infection prevalence of 57% in the term delivery group and 84% in the preterm delivery group, a sample size of 88 controls and 44 cases will be sufficient to detect the a difference in prevalence with 90% power and a=0.05. This sample size is also sufficient to detect the HPV prevalence in each group with +/-11% precision of the 95% confidence intervals.
In order to minimise introduction of selection bias participants will be recruited on a ‘first come first served’ basis, i.e. once we reached 44 cases and 88 controls, recruitment will cease. No selection of cases or controls will be made. Samples collected from women who presented in threatened PTL (TPTL), treated, and went on to deliver after 37 weeks of gestation will be analysed separately for the prevalence of HPV and will not be included as cases or controls to test the study’s stated objectives.
Analysis plan:
- HPV infection prevalence will be calculated with 95% confidence intervals.
- Chi-squared test will be used to compare the prevalence of HPV in both groups.
- Logistic regression will be used to investigate relationships between HPV infection, smoking, cervical smear history, and other confounders with the odds of preterm labour.
- Exploratory analysis will be carried out for prevalence estimates of the 30 different types of HPV the swab and placental sample are tested for, to inform future research planning.
- To test for agreement in HPV detection from different sites, kappa coefficients (chance-adjusted measures of agreement) will be calculated, along with percentages of agreement.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
30/01/2016
Date of last participant enrolment
Anticipated
30/06/2018
Actual
Date of last data collection
Anticipated
30/06/2018
Actual
Sample size
Target
200
Accrual to date
140
Final
Recruitment outside Australia
Country [1] 9581 0
New Zealand
State/province [1] 9581 0
Otago/Southland

Funding & Sponsors
Funding source category [1] 298657 0
Charities/Societies/Foundations
Name [1] 298657 0
Mercia Barnes Trust (RANZCOG)
Country [1] 298657 0
New Zealand
Funding source category [2] 298659 0
University
Name [2] 298659 0
University of Otago
Country [2] 298659 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Department of Women's and Children's Health and Department of Pathology
Dunedin School of Medicine
PO Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 297826 0
None
Name [1] 297826 0
Address [1] 297826 0
Country [1] 297826 0
Other collaborator category [1] 279932 0
Hospital
Name [1] 279932 0
Dunedin Public Hospital
Address [1] 279932 0
201 Great King St
Dunedin 9016
Country [1] 279932 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299612 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 299612 0
Health and Disability Ethics Committees
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 299612 0
New Zealand
Date submitted for ethics approval [1] 299612 0
12/08/2016
Approval date [1] 299612 0
26/08/2016
Ethics approval number [1] 299612 0
16/STH/128

Summary
Brief summary
The HIPPOP study is a case control study conducted at the University of Otago, Dunedin School of Medicine, Depts. of Women’s and Children’s Health and Pathology, to determine the prevalence of human papillomavirus (HPV) in the blood, placenta and cervix of women presenting in preterm labour (PTL) or preterm prelabour rupture of membranes (PPROM), and the association between placental HPV infection and PTL and PPROM. Overall, it will attempt to determine if placental HPV infection plays a role in preterm labour, raising the possibility of prediction of risk, and/or screening for PTL, and development of treatment to reduce the incident or prevent preterm labour.
Trial website
Trial related presentations / publications
Public notes
Please note, the recruitment numbers are different to those stated in the "Statistical methods/analysis" field in step 6 since we were unable to reach the required number of cases (PTL). The stated numbers are overall numbers and include both cases and controls. We either need to continue to recruit until we get to the required number of cases or stop at a point in time and do a 2:1 analysis as per the numbers of cases. However, we prefer to try and collect until we reach the number of cases and then potentially do a 3:1 analysis. We will reassess this situation around June 2018.

Contacts
Principal investigator
Name 81026 0
Dr Celia Devenish
Address 81026 0
Section of Obstetrics & Gynaecology
Department of Women's and Children's Health
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 81026 0
New Zealand
Phone 81026 0
+64-3-4709750
Fax 81026 0
Email 81026 0
[email protected]
Contact person for public queries
Name 81027 0
Dr Leehe Vardi
Address 81027 0
Section of Obstetrics & Gynaecology
Department of Women's and Children's Health
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 81027 0
New Zealand
Phone 81027 0
+64-3-4709750
Fax 81027 0
Email 81027 0
[email protected]
Contact person for scientific queries
Name 81028 0
Dr Noelyn Hung
Address 81028 0
Department of Pathology
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 81028 0
New Zealand
Phone 81028 0
+64-3-4709750
Fax 81028 0
Email 81028 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.