FeverNCT00398775
Procalcitonin in Fever of Unknown Etiology
A study testing antibiotic discontinuation in people with Fever, run by Changi General Hospital at 1 site in Singapore.
Trial summary
The purpose of this study is to determine whether new blood test (procalcitonin) can help to reduce unnecessary use of antibiotics in patients with unexplained fever. Although fever is most commonly caused by bacterial infection there are multiple other conditions that can cause fever. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Fever
- What is being tested?
- antibiotic discontinuation
- Type of treatment
- Surgery or procedure
- How many people
- 90 participants
- Where
- 1 siteSingapore
- Study dates
- Jan 2007to Sep 2007
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All hospitalized patients admitted to general medical or GRM wards with fever and no obvious source of infection, and
- remain febrile after 72 hours of empiric, antimicrobial therapy, and
- initial blood cultures are negative.
Who cannot join
- Patients with clinically suspected infection (strongly suggestive symptoms, signs or laboratory/imaging studies) such as pneumonia, urinary tract infection, meningitis, endocarditis, skin and soft tissue infection, etc.
- Confirmed bacterial, viral or fungal infection (positive stain, culture or serology from appropriate clinical specimen).
- Hypotension (systolic blood pressure <90mmHg)
- Respiratory failure (oxygen requirement > 4L/min via nasal canula)
- Patients admitted to intensive care unit.
- Severely immunocompromised patients: (febrile neutropenia, HIV infection with CD4 count < 200, immuno-suppressive therapy).
- Patients younger than 21.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Procalcitonin Guided Antimicrobial Discontinuation in Hospitalised Patients With Fever of Unknown Etiology
The purpose of this study is to determine whether new blood test (procalcitonin) can help to reduce unnecessary use of antibiotics in patients with unexplained fever.
Although fever is most commonly caused by bacterial infection there are multiple other conditions that can cause fever. It can be caused by viral infection. It can also be caused by other non infectious disease. Patients with malignancy, inflammation (such as gout or arthritis), or clots in veins can present with fever. Occasionally medications themselves can cause fever. If fever is not caused by infection antibiotics will not help. Instead they may cause side effects such as diarrhea and allergic reactions. We want to determine whether simple blood test (procalcitonin) can help us to make a difference between fever caused by infection and fever caused by others (above mentioned) non-infectious problems. We also want to determine whether such test would help us to reduce unnecessary antibiotic use and help us to find faster the real cause of the fever.
Read more
A total of 90 patients with the unexplained fever will be participating in this study. This study will involve single, additional blood test, performed only if patient continue to have fever despite a few days of investigations and therapy with antibiotics.
Patients will be assigned by drawing to one of two groups. In the first group blood test (procalcitonin) will help a doctor to decide whether to stop or continue antibiotics. If procalcitonin level is high antibiotics will be continued and the doctor will most probably order additional tests to determine the source of infection. If procalcitonin level is low serious bacterial infection is unlikely. The antibiotics will be stopped and a doctor will try to look for other cause of fever.
In the second group blood for the tests will be collected but not reported to a doctor. You will be treated in traditional manner by a doctor.
By following this procedure we will be able to determine whether therapy guided by procalcitonin level is as safe and possibly more effective than traditional approach. This study does not involve any other tests or study medications. We will attempt to contact all patients one month later by phone to determine whether you remain well after discharge.
Read the detailed description
Antimicrobial resistance has increasingly become a threat to patient safety in health care settings.1 Several studies have identified the inappropriate use of antimicrobials as important risk factor for antimicrobial resistance and the important area of opportunity for increasing patient safety and improving patient outcomes.2 High rates of antimicrobial use have been linked to high rates of antimicrobial resistance,3 and increased exposure to antimicrobials has been associated with an increased probability of colonization with resistant pathogens. It has also been shown that antimicrobial control results in significant cost savings4 and it may reduce antimicrobial resistance Surveys reveal that 25 - 33% of hospitalized patients receive antibiotics6 and that 22 - 65% of antibiotic use in hospitalized patients is inappropriate.7
Reasons for inappropriate antimicrobial therapy include:
- treating anybody with fever (even when it is not caused by infection) with broad spectrum antibiotics
- treating colonization or contamination (rather than real infection)
- continuing antibiotics even when infection was cured or is unlikely8
It is quite clear that clinicians need reliable marker for bacterial infections that would allow an early diagnosis, inform about the course and prognosis of the disease and facilitate therapeutic decisions.9 Procalcitonin covers these features better as compared to other, more commonly used biomarkers (such as CRP).10 It has been shown recently that procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia without compromising patients' safety. 11, 12 However, the efficacy and safety of PGAD in hospitalized patients with undefined fever has not been previously investigated.
We think that PGAD should be equally safe and effective intervention in hospitalized patients with fever of unknown etiology. It should help to reduce inappropriate antibiotic use and in effect, help to control antimicrobial resistance.
- Conditions
- Fever
- Being tested
- antibiotic discontinuation
- Keywords
- procalcitonin guided antibiotic discontinuation, fever of unknown origin
- Medical subject headings
- Fever, Fever of Unknown Origin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
antibiotic discontinuationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Exposure to systemic antimicrobial treatment:
duration of antibiotic treatment (in days).
total antibiotic exposure (in defined daily doses).
Secondary outcomes (5)
28-day case-fatality rate (in %)
Length of hospital stay (in days)
Costs of antimicrobial therapy (in SGD)
Rate of nosocomial super-infection (in N super-infections per 100 patients)
Isolation of multi-resistant microorganisms (in clinical isolates per 100 patient-days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2006 (estimated)
- Study startJan 2007
- Study completionSep 2007
Why it stopped: Very low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for FeverStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changi General Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Maciej P Chlebicki, MD, Principal investigator, Changi General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00398775
- Sponsor's protocol ID
- 2006/36
- Status last verified
- Nov 2007
- First submitted
- 13 Nov 2006
- Last updated
- 20 Nov 2007
- Results posted
- No
Publications
Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004 Feb 21;363(9409):600-7. doi: 10.1016/S0140-6736(04)15591-8.
PubMed 14987884Briel M, Christ-Crain M, Young J, Schuetz P, Huber P, Periat P, Bucher HC, Muller B. Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]. BMC Fam Pract. 2005 Aug 18;6:34. doi: 10.1186/1471-2296-6-34.
PubMed 16107222Christ-Crain M, Stolz D, Bingisser R, Muller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Muller B. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006 Jul 1;174(1):84-93. doi: 10.1164/rccm.200512-1922OC. Epub 2006 Apr 7.
PubMed 16603606Christ-Crain M, Muller B. Procalcitonin in bacterial infections--hype, hope, more or less? Swiss Med Wkly. 2005 Aug 6;135(31-32):451-60. doi: 10.4414/smw.2005.11169.
PubMed 16208582
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Procalcitonin Guided Antimicrobial Discontinuation in Hospitalised Patients With Fever of Unknown Etiology
- ClinicalTrials.gov ID
- NCT00398775
- Acronym / sponsor ID
- 2006/36
- Conditions
- Fever
- Keywords
- procalcitonin guided antibiotic discontinuation, fever of unknown origin
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Very low recruitment
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Changi General HospitalUniversity, hospital or other
- Study start
- Jan 2007
- Study completion
- Sep 2007 (actual)
- First posted
- 14 Nov 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether new blood test (procalcitonin) can help to reduce unnecessary use of antibiotics in patients with unexplained fever.
Although fever is most commonly caused by bacterial infection there are multiple other conditions that can cause fever. It can be caused by viral infection. It can also be caused by other non infectious disease. Patients with malignancy, inflammation (such as gout or arthritis), or clots in veins can present with fever. Occasionally medications themselves can cause fever. If fever is not caused by infection antibiotics will not help. Instead they may cause side effects such as diarrhea and allergic reactions. We want to determine whether simple blood test (procalcitonin) can help us to make a difference between fever caused by infection and fever caused by others (above mentioned) non-infectious problems. We also want to determine whether such test would help us to reduce unnecessary antibiotic use and help us to find faster the real cause of the fever.
A total of 90 patients with the unexplained fever will be participating in this study. This study will involve single, additional blood test, performed only if patient continue to have fever despite a few days of investigations and therapy with antibiotics.
Patients will be assigned by drawing to one of two groups. In the first group blood test (procalcitonin) will help a doctor to decide whether to stop or continue antibiotics. If procalcitonin level is high antibiotics will be continued and the doctor will most probably order additional tests to determine the source of infection. If procalcitonin level is low serious bacterial infection is unlikely. The antibiotics will be stopped and a doctor will try to look for other cause of fever.
In the second group blood for the tests will be collected but not reported to a doctor. You will be treated in traditional manner by a doctor.
By following this procedure we will be able to determine whether therapy guided by procalcitonin level is as safe and possibly more effective than traditional approach. This study does not involve any other tests or study medications. We will attempt to contact all patients one month later by phone to determine whether you remain well after discharge.
Detailed description
Antimicrobial resistance has increasingly become a threat to patient safety in health care settings.1 Several studies have identified the inappropriate use of antimicrobials as important risk factor for antimicrobial resistance and the important area of opportunity for increasing patient safety and improving patient outcomes.2 High rates of antimicrobial use have been linked to high rates of antimicrobial resistance,3 and increased exposure to antimicrobials has been associated with an increased probability of colonization with resistant pathogens. It has also been shown that antimicrobial control results in significant cost savings4 and it may reduce antimicrobial resistance Surveys reveal that 25 - 33% of hospitalized patients receive antibiotics6 and that 22 - 65% of antibiotic use in hospitalized patients is inappropriate.7
Reasons for inappropriate antimicrobial therapy include:
- treating anybody with fever (even when it is not caused by infection) with broad spectrum antibiotics
- treating colonization or contamination (rather than real infection)
- continuing antibiotics even when infection was cured or is unlikely8
It is quite clear that clinicians need reliable marker for bacterial infections that would allow an early diagnosis, inform about the course and prognosis of the disease and facilitate therapeutic decisions.9 Procalcitonin covers these features better as compared to other, more commonly used biomarkers (such as CRP).10 It has been shown recently that procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia without compromising patients' safety. 11, 12 However, the efficacy and safety of PGAD in hospitalized patients with undefined fever has not been previously investigated.
We think that PGAD should be equally safe and effective intervention in hospitalized patients with fever of unknown etiology. It should help to reduce inappropriate antibiotic use and in effect, help to control antimicrobial resistance.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- All hospitalized patients admitted to general medical or GRM wards with fever and no obvious source of infection, and
- remain febrile after 72 hours of empiric, antimicrobial therapy, and
- initial blood cultures are negative.
Key exclusion criteria (7 listed)
- Patients with clinically suspected infection (strongly suggestive symptoms, signs or laboratory/imaging studies) such as pneumonia, urinary tract infection, meningitis, endocarditis, skin and soft tissue infection, etc.
- Confirmed bacterial, viral or fungal infection (positive stain, culture or serology from appropriate clinical specimen).
- Hypotension (systolic blood pressure <90mmHg)
- Respiratory failure (oxygen requirement > 4L/min via nasal canula)
- Patients admitted to intensive care unit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| antibiotic discontinuation | Procedure or surgery | – |
Primary outcome
Exposure to systemic antimicrobial treatment:
duration of antibiotic treatment (in days).
total antibiotic exposure (in defined daily doses).
5 secondary outcomes
28-day case-fatality rate (in %)
Length of hospital stay (in days)
Costs of antimicrobial therapy (in SGD)
Rate of nosocomial super-infection (in N super-infections per 100 patients)
Isolation of multi-resistant microorganisms (in clinical isolates per 100 patient-days)
Results and safety
The study was stopped early (reason given: Very low recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2007.
- Background: PubMed 14987884Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004 Feb 21;363(9409):600-7. doi: 10.1016/S0140-6736(04)15591-8.
- Background: PubMed 16107222Briel M, Christ-Crain M, Young J, Schuetz P, Huber P, Periat P, Bucher HC, Muller B. Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]. BMC Fam Pract. 2005 Aug 18;6:34. doi: 10.1186/1471-2296-6-34.
- Background: PubMed 16603606Christ-Crain M, Stolz D, Bingisser R, Muller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Muller B. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006 Jul 1;174(1):84-93. doi: 10.1164/rccm.200512-1922OC. Epub 2006 Apr 7.
- Background: PubMed 16208582Christ-Crain M, Muller B. Procalcitonin in bacterial infections--hype, hope, more or less? Swiss Med Wkly. 2005 Aug 6;135(31-32):451-60. doi: 10.4414/smw.2005.11169.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maciej P Chlebicki, MD principal investigator
Changi General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing antibiotic discontinuation in people with Fever, run by Changi General Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Nov 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Very low recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exposure to systemic antimicrobial treatment:. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00398775, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2007.