A Screening Strategy for Q Fever Among Pregnant Women

Q Fever Clinical Trial

Official title:

Cost-effectiveness of a Screening Strategy for Q Fever Among Pregnant Women in Risk Areas: a Clustered Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01095328
• Other study ID #: NL30340.042.09
• Status: Recruiting
• Phase: N/A
• First received: March 29, 2010
• Last updated: June 30, 2010
• Start date: March 2010
• Est. completion date: March 2011

Study information

• Verified date: February 2010
• Source: University Medical Center Groningen
• Contact: Eelko Hak, Dr
• Phone: +31 50 36 14616
• Email: E.Hak[@]epi.umcg.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: March 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Screening

Related Conditions & MeSH terms

• Fever
• Q Fever

Intervention

Other:
• screening
screening for Q-fever with a single blood sampling

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

References & Publications (19)

Advice Dutch Health Council, http://www.gezondheidsraad.nl/nl/adviezen/briefadviesbijeenkomst- over-q-koorts-nederland

Carcopino X, Raoult D, Bretelle F, Boubli L, Stein A. Managing Q fever during pregnancy: the benefits of long-term cotrimoxazole therapy. Clin Infect Dis. 2007 Sep 1;45(5):548-55. Epub 2007 Jul 17. — View Citation

Dupont HT, Thirion X, Raoult D. Q fever serology: cutoff determination for microimmunofluorescence. Clin Diagn Lab Immunol. 1994 Mar;1(2):189-96. — View Citation

Gikas A, Kofteridis DP, Manios A, Pediaditis J, Tselentis Y. Newer macrolides as empiric treatment for acute Q fever infection. Antimicrob Agents Chemother. 2001 Dec;45(12):3644-6. — View Citation

Hartzell JD, Wood-Morris RN, Martinez LJ, Trotta RF. Q fever: epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008 May;83(5):574-9. doi: 10.4065/83.5.574. Review. — View Citation

Jover-Díaz F, Robert-Gates J, Andreu-Gimenez L, Merino-Sanchez J. Q fever during pregnancy: an emerging cause of prematurity and abortion. Infect Dis Obstet Gynecol. 2001;9(1):47-9. — View Citation

Karagiannis I, Morroy G, Rietveld A, Horrevorts AM, Hamans M, Francken P, Schimmer B. Q fever outbreak in the Netherlands: a preliminary report. Euro Surveill. 2007 Aug 9;12(8):E070809.2. — View Citation

Langley JM, Marrie TJ, Leblanc JC, Almudevar A, Resch L, Raoult D. Coxiella burnetii seropositivity in parturient women is associated with adverse pregnancy outcomes. Am J Obstet Gynecol. 2003 Jul;189(1):228-32. — View Citation

Lin JM, Brimmer DJ, Maloney EM, Nyarko E, Belue R, Reeves WC. Further validation of the Multidimensional Fatigue Inventory in a US adult population sample. Popul Health Metr. 2009 Dec 15;7:18. doi: 10.1186/1478-7954-7-18. — View Citation

Maurin M, Raoult D. Q fever. Clin Microbiol Rev. 1999 Oct;12(4):518-53. Review. — View Citation

McCaughey C, McKenna J, McKenna C, Coyle PV, O'Neill HJ, Wyatt DE, Smyth B, Murray LJ. Human seroprevalence to Coxiella burnetii (Q fever) in Northern Ireland. Zoonoses Public Health. 2008 May;55(4):189-94. doi: 10.1111/j.1863-2378.2008.01109.x. — View Citation

Meekelenkamp JCE, Notermans DW, Rietveld A, Marcelis JH, Schimmer B, Reimerink JHJ, Vollebergh JHA, Wijkmans CJ, Leenders ACAP. Seroprevalence of Coxiella burnetii in pregnant women in the province of Noord-Brabant in 2007. Infectieziekten Bulletin, 20: 57-61 [in Dutch].

Parker NR, Barralet JH, Bell AM. Q fever. Lancet. 2006 Feb 25;367(9511):679-88. Review. — View Citation

Raoult D, Fenollar F, Stein A. Q fever during pregnancy: diagnosis, treatment, and follow-up. Arch Intern Med. 2002 Mar 25;162(6):701-4. — View Citation

Schimmer B, Morroy G, Dijkstra F, Schneeberger PM, Weers-Pothoff G, Timen A, Wijkmans C, van der Hoek W. Large ongoing Q fever outbreak in the south of The Netherlands, 2008. Euro Surveill. 2008 Jul 31;13(31). pii: 18939. — View Citation

Stein A, Raoult D. Q fever during pregnancy: a public health problem in southern France. Clin Infect Dis. 1998 Sep;27(3):592-6. Review. — View Citation

Vaidya VM, Malik SV, Kaur S, Kumar S, Barbuddhe SB. Comparison of PCR, immunofluorescence assay, and pathogen isolation for diagnosis of q fever in humans with spontaneous abortions. J Clin Microbiol. 2008 Jun;46(6):2038-44. doi: 10.1128/JCM.01874-07. Epub 2008 Apr 30. — View Citation

Van Steenbergen JE, Morroy G, Groot CA, Ruikes FG, Marcelis JH, Speelman P. [An outbreak of Q fever in The Netherlands--possible link to goats]. Ned Tijdschr Geneeskd. 2007 Sep 8;151(36):1998-2003. Dutch. — View Citation

Wagner-Wiening C, Brockmann S, Kimmig P. Serological diagnosis and follow-up of asymptomatic and acute Q fever infections. Int J Med Microbiol. 2006 May;296 Suppl 40:294-6. Epub 2006 Mar 9. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	obstetric or maternal complications in Q fever positive women	Presence of any obstetric or maternal complication after the first trimester of pregnancy, i.e. spontaneous abortion, intrauterine fetal death, termination of pregnancy, oligohydramnios, premature delivery or intrauterine growth retardation. Spontaneous abortion is defined as spontaneous expulsion of the embryo or the fetus before 16 weeks of gestation. Oligohydramnios is defined as the ultrasonic measurement with an amniotic index <=5 cm. IUGR is defined as a fetal birth weight less than the 10th percentile for gestational age, according to the national reference curves.	obstetric complications till delivery, maternal till one month post partum	No
Secondary	course of infection in pregnant women	maternal chronic infection or reactivation	till one month post partum	No
Secondary	the accuracy of the diagnostic tests used for screening	the accuracy of the diagnostic tests used for screening (serology vs PCR)	around 20 weeks of gestation	No
Secondary	placentitis	the extent to which the placenta has been infected	one month post partum	No
Secondary	costs	The costs associated with health care consumption and other related costs among pregnant women.	till one month post partum	No