Clinical trial NCT01095328: A Screening Strategy for Q Fever Among Pregnant Women
Official title: Cost-effectiveness of a Screening Strategy for Q Fever Among Pregnant Women in Risk Areas: a Clustered Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Q Fever
Keywords: Q fever
Pregnancy
Screening
Cost-effectiveness
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2010-03-30
Enrollment: 4000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: Q fever in the Netherlands is becoming more common. A Q fever infection is a serious threat to certain risk groups,including pregnant women. Pregnant women are more often than the general population asymptomatic. Studies from France show that an infection with Coxiella burnetii may cause obstetric complications including spontaneous abortion, intrauterine fetal death, intrauterine growth retardation and oligohydramnios.

The aim of this study is to assess the effectiveness and cost effectiveness of a multidisciplinary screening program, whereby pregnant women in first line healthcare in high-risk areas for Q fever are screened with a single blood sample during pregnancy. If found positive for Q fever, advise for antibiotic treatment will follow as part of regular healthcare. Treatment is therefore not part of the study protocol.

The results of this study will give more insights in the risks of asymptomatic Q fever in pregnancy and the benefits and harms of a screening strategy during pregnancy. This study will be used to give an evidence based advice to the Dutch minister of health on screening for Q fever in pregnancy.

Detailed description: We will conduct a clustered randomized controlled trial among pregnant women within an area of high transmission. The study participants will be recruited by the midwives in high risk areas, defined by postal code from the RIVM. To inform the public in this area about the study we will publish an article in local newspapers. The midwife centers will be randomized to recruit pregnant women for either the control group or the intervention group. The pregnant women will receive study information by mail using the midwives patients file. It is estimated that approximately 10,000 eligible women live in the areas of transmission. After written informed consent, they will start with the strategy for which the midwife center is randomized.

Participants will be asked for a blood sample in their second trimester of pregnancy, possibly combined with the routine structural ultrasound around 20 weeks of pregnancy to minimize hospital visit. If participants are enrolled in their third trimester, they will have their blood sampling as soon as possible after inclusion.

When taking part in the intervention group the sample will be tested immediately for Q fever. If found positive for acute or chronic Q fever, patients have to be referred, according to local protocol, to a hospital for further pregnancy monitoring and long-term bacteriostatic treatment. Follow-up blood samples are required at 14 days, 3, 6 and 12 months after the first blood sampling as part of the standardized control of Q fever disease to diagnose possible chronicity of infection. Furthermore, current routine for pregnant women being treated with antibiotics against Q fever is to perform monthly blood analyses to monitor treatment, and if the serological parameters descend, these controls are brought back to once every two months. According to local protocol patients with Q fever have to deliver in hospital. After pregnancy serology should be continued with check-ups at 3, 6 and 12 months following the current protocol. Furthermore, after delivery a bacteriocide treatment with doxycycline or an alternative will be started by the specialist as part of regular health care.

In the control arm the blood samples will be stored, and analyzed for Q fever after delivery. If tested positive for Q fever after pregnancy antibiotics could be started if needed as part of regular health care.

At baseline, a questionnaire will be administered to all participants asking about the current pregnancy , pregnancy outcome of any previous pregnancies and demographics. Further risk factors for pregnancy outcome will also be obtained such as smoking and drinking behavior, risk-elevating comorbidities and medication use.

After delivery all relevant outcome data will be collected by questionnaires filled out by the midwife, GP or specialist after delivery, notably the presence of obstetric complications. One month after delivery or end of pregnancy, a last questionnaire will be administered to the participant to verify potential long-term consequences of Q fever, potential loss of income, health-related quality-of-life, fatigue and depressive symptoms. Furthermore questions will be asked about the condition of the newborn and risk-accessing questions for Q fever infection will be asked.

In the context of the secondary research questions an extra blood sample will be required, and placentas as well as amniotic fluid will be collected after delivery. The latter will only take place in a limited number of women and only if they gave birth in a hospital.

All participants will receive usual care and will be asked to visit the general practitioner if symptoms of Q fever occur. He/she will start diagnostic research and treatment or will refer the patient to the hospital. Furthermore, both arms have access to an expert team for support.

Eligibility criteria: Inclusion Criteria:

* being pregnant under first line healthcare
* being eighteen years or older
* having signed an informed consent form
* having a estimated date of delivery between June 1th 2010 en December 31th 2010

Exclusion Criteria:

* unable to fulfill study procedures
* absence of informed consent
* have been tested positive for Q fever prior to pregnancy
* unable to understand Dutch

Primary outcomes:
measure: obstetric or maternal complications in Q fever positive women
timeFrame: obstetric complications till delivery, maternal till one month post partum
Secondary outcomes:
measure: course of infection in pregnant women
timeFrame: till one month post partum
measure: the accuracy of the diagnostic tests used for screening
timeFrame: around 20 weeks of gestation
measure: placentitis
timeFrame: one month post partum
measure: costs
timeFrame: till one month post partum
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Eelko Hak, Dr.
role: STUDY_DIRECTOR
affiliation: University Medical Center Groningen
name: Janna Munster, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Infectious Disease Control
name: Wim van der Hoek, Drs.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: Ronald Stolk, Prof. dr.
role: STUDY_CHAIR
affiliation: University Medical Center Groningen
name: Jan Aarnoudse, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Jeroen Bosch Hospital
name: Sander Leenders, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: Bert Timmer, Dr.
role: PRINCIPAL_INVESTIGATOR
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