Ventilator Associated PneumoniaNCT03982667
Research Title: Efficacy and Safety of Point- Of-care Procalcitonin Test to Reduce Antibiotic Exposure in VAP
A study testing PCT-guided group in people with Ventilator Associated Pneumonia, run by Mohd Zulfakar Mazlan, MBBS at 2 sites in Malaysia.
Trial summary
Several studies have shown that PCT guidance can reduce the duration of antibiotic treatment for patients with bacterial infections in the ICU, without compromising the safety outcomes. However PCT is known to be more costly than standard biomarkers that commonly use in our ICU setup. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventilator Associated Pneumonia
- What is being tested?
- PCT-guided group
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesMalaysia
- Study dates
- 15 Jun 2019to 1 Jul 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years and above; and
- Admitted to the ICU; and
- Receive their first dose of antibiotics no longer than 24 h before inclusion to the trial for an assumed or proven bacterial infection.
- Treated as Ventilator Associated Pneumonia (VAP)
Who cannot join
- Systemic antibiotics as prophylaxis only
- Antibiotics solely as part of selective decontamination of the digestive tract
- Prolonged therapy (eg, endocarditis)
- Expected ICU stay of less than 24 h
- Severe immunosuppression
- Severe infections due to non-bacterial causes
- Previously been enrolled in the study
Trial locations and contacts
2 sites in 1 country.
Malaysia2 sites
Mohd Zulfakar Mazlan, MBBS
Kota Bharu, Kelantan, 16150
Mohd Zulfakar Mazlan
Kota Bharu, Kelantan, 16150
About this study
Official title: Research Title: Efficacy and Safety of Point- Of-care Procalcitonin Test to Reduce Antibiotic Exposure in Ventilator Associated Pneumonia (VAP) Patient in ICU: A Randomised Controlled Trial
Several studies have shown that PCT guidance can reduce the duration of antibiotic treatment for patients with bacterial infections in the ICU, without compromising the safety outcomes. However PCT is known to be more costly than standard biomarkers that commonly use in our ICU setup. This remain the main challenge for us whether by monitoring the PCT level, it can reduce both the duration of antibiotic simultaneously reduce the total cost of the treatment for the patients. A local study addressing efficacy, safety and cost analysis of PCT-guided antibiotic therapy in severe pneumonia patients is therefore warranted. Until the results from a local study become available, the utility of PCT to guide antibiotic duration in our patient population cannot be recommended.
Read the detailed description
Pneumonia remains one of the major cause of morbidity and mortality in critically ill patients in the intensive care unit (ICU) worldwide. In Malaysia, according to the Malaysian Registry of Intensive Care 2016, pneumonia was among the four (5.7%) most common diagnosis leading to admission to ICU. In many scenario, pneumonia associated with severe sepsis either as single source of sepsis or in combination with other source of infection which carry mortality mortality reported 53.4% 1. Timely, appropriate and adequate antibiotic therapy is of paramount importance in the critically ill patients with severe pneumonia. However, overly long antibiotic treatment is undesirable because of side effects, increasing antibiotic resistance2 and financial burden to patient and Malaysia Healthcare.
Antibiotic remain the main weapon to combat pneumonia. Nevertheless, rampant use of antibiotic without specific indicator is vain. Hence, with the latest technology, physicians not only rely on clinical improvement but also specific biomarkers for resolution of sepsis which might assist the ICU physicians in making decisions on antibiotic therapy on an individual basis.
Commonest used biomarkers for this purpose include leucocyte count and C-reactive protein (CRP). These biomarkers are sensitive but not specific. Procalcitonin (PCT) however has been advocated as a biomarker with a better specificity and sensitivity for diagnosis and follow-up of severe bacterial infections.
PCT is the prohormone of calcitonin. It consists of about 116 amino-acids. The locus of formation in classical pathway is the C-cells of the thyroid. In case of bacterial infection, PCT is formed in all tissues via an alternative pathway. Linscheid et al. 2004 described, in case of bacterial infection two mechanisms of synthesis are at work. At first cytokine-stimulated adherent monocytes release PCT in low quantities. This synthesis is limited. But it plays an important role in the initiation of PCT synthesis in storage tissues of humans. This PCT burst is initiated in all storage tissues (>18h). PCT is a perfect tool to differentiate between viral and bacterial infections (e.g. Gendrel et al. 1999). This is why in septic patients extremely high concentrations of PCT were found in the plasma (about 100,000-fold of the physiological concentration in healthy subjects).
- Conditions
- Ventilator Associated Pneumonia
- Being tested
- PCT-guided group
- Medical subject headings
- Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCT-guided groupDiagnostic test
In the PCT-guided group, the study protocol encourages to stop the prescribed antibiotics if PCT concentration decrease by 80% or more of its peak value (or if PCT concentration is ≥0·25 and <0·5 μg/L), and strongly encourage to stop the prescribed antibiotics when it reaches a value of < 0·25 μg/L. The attending physician is free to decide whether to continue antibiotic treatment in patients who reach these thresholds. Reasons for non-adherence will be recorded. Antibiotics in the standard-of-care group will be stopped according to local or national guidelines and according to the discretion of attending physicians. Patients will be followed-up until hospital discharge.
| Study group | Role | What they receive |
|---|---|---|
| PCT group | Experimental | For patients randomly assigned to the PCT-guided group, measurements of serum PCT concentrations (Day 1, 3, 7, and 9) will be taken and made available to the attending physicians. This means 3 ml of whole blood will be sampled from the arterial line of the patients for each measurement the serum PCT in plain tubes. The samples will be immediately assayed for the PCT measurement using the available device and the results will be ready in next 30 minutes after running the system. Receives: Diagnostic Test: PCT-guided group |
| Standard-of-care group | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the duration of antibiotic treatment between PCT and standard of care groups
Most of the antiobiotic duration is about 5 - 14 days. In Ventilated Associated Pneumonia, the duration of antibiotic treatment is difficult to stop since the patient stil in intensive care unit due to multiple factors. Therefore the use of PCT guided might be useful.
Measured: 3 to 14 days
Secondary outcomes (2)
To compare the mortality between PCT and standard of care
Malaysia Sepsis Mortality rate is nearly 50%. This could be because of higher APACHE score. In PCT guided group, the antibiotic might be stop earlier if clinically indicated. Therefore, the rate of patient die in this group is very important to assess the safety of using this point of care PCT in ICU.
Measured: 30 days
To compare the rate of recurrence infection between PCT and standard of care
By stopping antibiotics earlier, the is possibility risk of recurrent infection if the source of infection is not adequately treated. Therefore the number of recurrence infection is required in PCT group to assess the safety of using PCT guided antibiotic in ICU
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2019
- Study start15 Jun 2019
- Primary completion1 Jul 2020
- Study completion1 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ventilator Associated PneumoniaStudies 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
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mohd Zulfakar Mazlan, MBBS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mohd Zulfakar Mazlan, MBBS, Universiti Sains Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03982667
- Sponsor's protocol ID
- USMalaysia
- Status last verified
- Jul 2020
- First submitted
- 8 Jun 2019
- Last updated
- 15 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Research Title: Efficacy and Safety of Point- Of-care Procalcitonin Test to Reduce Antibiotic Exposure in Ventilator Associated Pneumonia (VAP) Patient in ICU: A Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT03982667
- Acronym / sponsor ID
- USMalaysia
- Conditions
- Ventilator Associated Pneumonia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Mohd Zulfakar Mazlan, MBBSUniversity, hospital or other
- Study start
- 15 Jun 2019 (actual)
- Primary completion
- 1 Jul 2020 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 11 Jun 2019 (actual)
- 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.
Several studies have shown that PCT guidance can reduce the duration of antibiotic treatment for patients with bacterial infections in the ICU, without compromising the safety outcomes. However PCT is known to be more costly than standard biomarkers that commonly use in our ICU setup. This remain the main challenge for us whether by monitoring the PCT level, it can reduce both the duration of antibiotic simultaneously reduce the total cost of the treatment for the patients. A local study addressing efficacy, safety and cost analysis of PCT-guided antibiotic therapy in severe pneumonia patients is therefore warranted. Until the results from a local study become available, the utility of PCT to guide antibiotic duration in our patient population cannot be recommended.
Detailed description
Pneumonia remains one of the major cause of morbidity and mortality in critically ill patients in the intensive care unit (ICU) worldwide. In Malaysia, according to the Malaysian Registry of Intensive Care 2016, pneumonia was among the four (5.7%) most common diagnosis leading to admission to ICU. In many scenario, pneumonia associated with severe sepsis either as single source of sepsis or in combination with other source of infection which carry mortality mortality reported 53.4% 1. Timely, appropriate and adequate antibiotic therapy is of paramount importance in the critically ill patients with severe pneumonia. However, overly long antibiotic treatment is undesirable because of side effects, increasing antibiotic resistance2 and financial burden to patient and Malaysia Healthcare.
Antibiotic remain the main weapon to combat pneumonia. Nevertheless, rampant use of antibiotic without specific indicator is vain. Hence, with the latest technology, physicians not only rely on clinical improvement but also specific biomarkers for resolution of sepsis which might assist the ICU physicians in making decisions on antibiotic therapy on an individual basis.
Commonest used biomarkers for this purpose include leucocyte count and C-reactive protein (CRP). These biomarkers are sensitive but not specific. Procalcitonin (PCT) however has been advocated as a biomarker with a better specificity and sensitivity for diagnosis and follow-up of severe bacterial infections.
PCT is the prohormone of calcitonin. It consists of about 116 amino-acids. The locus of formation in classical pathway is the C-cells of the thyroid. In case of bacterial infection, PCT is formed in all tissues via an alternative pathway. Linscheid et al. 2004 described, in case of bacterial infection two mechanisms of synthesis are at work. At first cytokine-stimulated adherent monocytes release PCT in low quantities. This synthesis is limited. But it plays an important role in the initiation of PCT synthesis in storage tissues of humans. This PCT burst is initiated in all storage tissues (>18h). PCT is a perfect tool to differentiate between viral and bacterial infections (e.g. Gendrel et al. 1999). This is why in septic patients extremely high concentrations of PCT were found in the plasma (about 100,000-fold of the physiological concentration in healthy subjects).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PCT group | Experimental | Diagnostic Test: PCT-guided groupFor patients randomly assigned to the PCT-guided group, measurements of serum PCT concentrations (Day 1, 3, 7, and 9) will be taken and made available to the attending physicians. This means 3 ml of whole blood will be sampled from the arterial line of the patients for each measurement the serum PCT in plain tubes. The samples will be immediately assayed for the PCT measurement using the available device and the results will be ready in next 30 minutes after running the system. |
| Standard-of-care group | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 years and above; and
- Admitted to the ICU; and
- Receive their first dose of antibiotics no longer than 24 h before inclusion to the trial for an assumed or proven bacterial infection.
- Treated as Ventilator Associated Pneumonia (VAP)
Key exclusion criteria (7 listed)
- Systemic antibiotics as prophylaxis only
- Antibiotics solely as part of selective decontamination of the digestive tract
- Prolonged therapy (eg, endocarditis)
- Expected ICU stay of less than 24 h
- Severe immunosuppression
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 |
|---|---|---|
| PCT-guided groupIn the PCT-guided group, the study protocol encourages to stop the prescribed antibiotics if PCT concentration decrease by 80% or more of its peak value (or if PCT concentration is ≥0·25 and <0·5 μg/L), and strongly encourage to stop the prescribed antibiotics when it reaches a value of < 0·25 μg/L. The attending physician is free to decide whether to continue antibiotic treatment in patients who reach these thresholds. Reasons for non-adherence will be recorded. Antibiotics in the standard-of-care group will be stopped according to local or national guidelines and according to the discretion of attending physicians. Patients will be followed-up until hospital discharge. | Diagnostic test | PCT group |
Primary outcome
To compare the duration of antibiotic treatment between PCT and standard of care groups
Time frame: 3 to 14 days
Most of the antiobiotic duration is about 5 - 14 days. In Ventilated Associated Pneumonia, the duration of antibiotic treatment is difficult to stop since the patient stil in intensive care unit due to multiple factors. Therefore the use of PCT guided might be useful.
2 secondary outcomes
To compare the mortality between PCT and standard of care
Time frame: 30 days
To compare the rate of recurrence infection between PCT and standard of care
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PCT-guided group in people with Ventilator Associated Pneumonia, run by Mohd Zulfakar Mazlan, MBBS at 2 sites in Malaysia.
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 4 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: finished, as of the sponsor's last update on 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Malaysia. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To compare the duration of antibiotic treatment between PCT and standard of care groups (time frame: 3 to 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jul 2020.