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.
Approximately 20% of patients with acute Q fever will develop chronic fatigue, referred to as Q fever fatigue syndrome (QFS). The objective of this randomized controlled clinical trial was to assess the efficacy of either long-term treatment with doxycycline or cognitive-behavioral therapy (CBT) in reducing fatigue severity in patients with QFS.



Adult patients were included who met the QFS criteria according to the Dutch guideline: a new onset of severe fatigue lasting ≥6 months with significant disabilities, related to an acute Q fever infection, without other somatic or psychiatric comorbidity explaining the fatigue. Using block randomization, patients were randomized between oral study medication and CBT (2:1) for 24 weeks. Second, a double-blind randomization between doxycycline (200 mg/day, once daily) and placebo was performed in the medication group. Primary outcome was fatigue severity at end of treatment (EOT; week 26), assessed with the Checklist Individual Strength subscale Fatigue Severity.



Of 155 patients randomized, 154 were included in the intention-to-treat analysis (doxycycline, 52; placebo, 52; CBT, 50). At EOT, fatigue severity was similar between doxycycline (40.8 [95% confidence interval {CI}, 37.3-44.3]) and placebo (37.8 [95% CI, 34.3-41.2]; difference, doxycycline vs placebo, -3.0 [97.5% CI, -8.7 to 2.6]; P = .45). Fatigue severity was significantly lower after CBT (31.6 [95% CI, 28.0-35.1]) than after placebo (difference, CBT vs placebo, 6.2 [97.5% CI, .5-11.9]; P = .03).



CBT is effective in reducing fatigue severity in QFS patients. Long-term treatment with doxycycline does not reduce fatigue severity in QFS patients compared to placebo.



NCT01318356.
Radboud Expertise Center for Q Fever, Nijmegen, The Netherlands.|Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, Nijmegen,  The Netherlands.
Stephan P
SP
Keijmel
Department of Internal Medicine, Medical Spectrum Twente, Enschede, The Netherlands.
Corine E
CE
Delsing
Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Gijs
G
Bleijenberg
Radboud Expertise Center for Q Fever, Nijmegen, The Netherlands.|Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, Nijmegen,  The Netherlands.
Jos W M
JWM
van der Meer
Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
Rogier T
RT
Donders
Department of Internal Medicine, Bernhoven Hospital, Uden, The Netherlands.
Monique
M
Leclercq
Department of Internal Medicine, Medical Center Leeuwarden, The Netherlands.
Linda M
LM
Kampschreur
Q-uestion, Foundation for Patients With Q Fever, Eindhoven, The Netherlands.
Michel
M
van den Berg
Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, Nijmegen,  The Netherlands.|Department of Internal Medicine,  Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands.
Tom
T
Sprong
Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
Marrigje H
MH
Nabuurs-Franssen
Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.|Department of Medical Psychology, Academic Medical Center, University of Amsterdam, The Netherlands.
Hans
H
Knoop
Radboud Expertise Center for Q Fever, Nijmegen, The Netherlands.|Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, Nijmegen,  The Netherlands.
Chantal P
CP
Bleeker-Rovers
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D015673:Fatigue Syndrome, Chronic / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010919:Placebos / Q000008:administration & dosage; D011778:Q Fever / Q000150:complications*; D016896:Treatment Outcome; D055815:Young Adult
D000900:Anti-Bacterial Agents; D010919:Placebos; D004318:Doxycycline
Coxiella burnetii; Q fever fatigue syndrome.; cognitive-behavioral therapy; doxycycline; placebo