Clinical trial NCT01318356: The Qure Study: Q-fever Fatigue Syndrome - Response to Treatment
Official title: The Qure Study: Q-fever Fatigue Syndrome - Response to Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Q Fever
Fatigue Syndrome, Chronic
Coxiella Infection
Keywords: Q fever
Cognitive behavioral therapy
Doxycycline
Fatigue
Coxiella
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2011-03-18
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the efficacy of two treatment strategies for fatigue and disabilities in QFS: long term treatment with doxycycline or cognitive behavioral therapy (CBT).

Detailed description: Q fever fatigue syndrome (QFS) is one of the most frequent sequelae of Q fever, and constitutes a significant problem in the current outbreak of Q fever. QFS leads to substantial morbidity and has a high socio-economic burden, related to increased use of healthcare facilities and absence from work. It is envisaged that over 750 patients will become chronically fatigued due to Q fever in The Netherlands (20% of 4000 patients from 2007 until now). Although the outbreak appears to diminish, it is expected that Q fever will remain an endemic disease, and therefore this number will continue to grow. A vast medical consumption can be anticipated, stressing the need for an accessible and effective intervention and clear treatment guidelines.

The study will contribute to a better understanding of effective treatment of QFS, providing evidence-based guidelines for general practitioners and medical specialists.

Eligibility criteria: Inclusion Criteria:

* Males or non-pregnant, non-lactating females who are 18 years or older
* Laboratory-proven acute Q fever since the year 2007 and/or positive serology fitting a past infection with Coxiella burnetii;
* AND being severely fatigued, defined by scoring 35 or higher on the subscale fatigue severity of the CIS;
* AND being fatigued for at least 6 months;
* AND disabled because of the fatigue, defined by scoring 450 or higher on the SIP
* Subjects must sign a written informed consent form.

Exclusion Criteria:

* Fulfilling criteria for chronic Q fever, namely:

  * IFA IgG fase I ≥ 1024, ≥ 3 months after acute Q fever and/or
  * Positive Coxiella burnetii PCR on serum or tissue, 1 month after acute Q fever
* Acute Q fever in the setting of a prosthetic cardiac valve or aneurysm surgery or stenting necessitating prophylactic use of doxycycline;
* Pregnancy or unwillingness to use effective contraceptives during the entire study period;
* Imminent death;
* Inability to give informed consent;
* Allergy or intolerance to doxycycline;
* Somatic or psychiatric illness that could explain the chronic fatigue;
* Subjects who are currently enrolled on other investigational drug trials or receiving investigational agents;
* Receiving antibiotics for more than 4 weeks, potentially active against Coxiella burnetii, for any other reason since Q-fever diagnosis;
* Subjects who are receiving and cannot discontinue barbiturates, phenytoin, or carbamazepine (these drugs may increase the metabolism of doxycycline and therefore reducing half-life of doxycycline);
* Moderate or severe liver disease (AF, ALAT, ASAT \> 3 times the upper limit of normal).
* Current engagement in a legal procedure concerning financial benefits (only current involvement interferes with the effectivity of cognitive behavioral therapy. Once the appeal procedure ends, subjects can be included)

Primary outcomes:
measure: Checklist Individual Strength (CIS)
timeFrame: 24 weeks after start of treatment
Secondary outcomes:
measure: Sickness Impact Profile (SIP) Total Score
timeFrame: 24 weeks after start of treatment
measure: Symptom Checklist 90 (SCL90)
timeFrame: 24 weeks after start of treatment
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud university medical center
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Chantal P Bleeker-Rovers, MD PhD
role: STUDY_DIRECTOR
References:
citation: Keijmel SP, Delsing CE, Sprong T, Bleijenberg G, van der Meer JW, Knoop H, Bleeker-Rovers CP. The Qure study: Q fever fatigue syndrome--response to treatment; a randomized placebo-controlled trial. BMC Infect Dis. 2013 Mar 27;13:157. doi: 10.1186/1471-2334-13-157.
citation: Keijmel SP, Delsing CE, Bleijenberg G, van der Meer JWM, Donders RT, Leclercq M, Kampschreur LM, van den Berg M, Sprong T, Nabuurs-Franssen MH, Knoop H, Bleeker-Rovers CP. Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome (Qure Study): A Randomized Controlled Trial. Clin Infect Dis. 2017 Apr 15;64(8):998-1005. doi: 10.1093/cid/cix013.