Clinical Trials Register

Summary
EudraCT Number:	2011-000643-25
Sponsor's Protocol Code Number:	205520003
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-02-10
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2011-000643-25

A.3

Full title of the trial

The Qure study: Q-fever fatigue syndrome - response to treatment

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

The Qure study: Q-fever fatigue syndrome - response to treatment

A.3.2

Name or abbreviated title of the trial where available

The Qure study

A.4.1

Sponsor's protocol code number

205520003

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01318356

A.5.4

Other Identifiers

Name:

Nederlands Trial Register (NTR)

Number:

NTR2797

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Radboud University Nijmegen Medical Centre
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ZonMW, The Netherlands Organisation for Health Research and Development
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Radboud University Nijmegen Medical Centre
B.5.2	Functional name of contact point	Department of Internal Medicine
B.5.3	Address:
B.5.3.1	Street Address	Postbus 9101
B.5.3.2	Town/ city	Nijmegen
B.5.3.3	Post code	6500 HB
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31243668256
B.5.5	Fax number	+31243541734
B.5.6	E-mail	S.Keijmel@aig.umcn.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Doxycycline Disp 100 PCH
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmachemie
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Doxycycline
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	17086-28-1
D.3.9.3	Other descriptive name	DOXYCYCLINE MONOHYDRATE
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Q fever fatigue syndrome (QFS) is one of the most frequent sequelae of Q fever. QFS leads to substantial morbidity, a high socio-economic burden and an increased use of healthcare facilities. QFS:
• Complaints of severe fatigue defined as scoring 35 or higher on the subscale for fatigue severity (CIS)
• Being fatigued for > 6 months
• Being disabled because of fatigue (SIP score 450 or higher)
• No somatic/psychiatric co-morbidity that could explain the chronic fatigue.

E.1.1.1

Medical condition in easily understood language

Q fever fatigue syndrome is one of the most frequent sequelae of Q fever with complaints of severe fatigue for > 6 months.

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10037688
E.1.2	Term	Q fever
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10008874
E.1.2	Term	Chronic fatigue syndrome
E.1.2	System Organ Class	10018065 - General disorders and administration site conditions

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of two treatment strategies for fatigue and disabilities in QFS: long term treatment with doxycycline or cognitive behavioral therapy (CBT). Both interventions will be compared to a placebo group. Primary outcome measure will be fatigue severity measured with the Checklist Individual Strength (CIS).

E.2.2

Secondary objectives of the trial

Secondary outcome measures will be:
•Level of functional impairment measured with the Sickness Impact Profile (SIP) total score;
•Level of psychological distress measured with the total score of the Symptom Checklist 90 (SCL90). The SCL90 consists of 90 items scored on a 5-point scale. Scores range from 90 to 450. A low total score reflects high psychological well-being. The SCL-90 is a reliable and valid instrument
•Coxiella serology and PCR (peripheral blood).

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal exclusion criteria

•Fulfilling criteria for chronic 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)

E.5 End points

E.5.1

Primary end point(s)

Primary outcome measure will be fatigue severity measured with the CIS.

E.5.1.1

Timepoint(s) of evaluation of this end point

Primary outcome will be measured 24 weeks after start treatment.

E.5.2

Secondary end point(s)

Secondary outcome measures will be:
•Level of functional impairment measured with the SIP;
•Level of psychological distress measured with the SCL90;
•Coxiella serology and PCR.

E.5.2.1

Timepoint(s) of evaluation of this end point

Level of functional impairment and the level of psychological distress will be measured 24 weeks after start treatment. Coxiella serology and PCR will be measured 26 weeks after start treatment.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study is defined as the last patient’s last visit.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2011-02-10.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

120

F.4.2.2

In the whole clinical trial

120

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

If patients still have complaints after completion or after withdrawal, regardless of the circumstances, patients are still able to be treated with cognitive behavioral therapy according to the standard patientcare.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-02-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-04-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-09-10

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