Acute Febrile IllnessCREATIBNCT05292508
Comparison of Rates of Antimicrobial Use in Febrile Patients With or Without the Use of C-reactive Protein Blood Test
A study testing C-reactive Protein Rapid Diagnostic Test in people with Acute Febrile Illness and Use of Antimicrobial Agents, run by Patan Academy of Health Sciences at 1 site in Nepal.
Trial summary
In Health Posts of rural areas operated by the Government of Nepal, there are limitations of tests to differentiate between bacterial and viral infections. Due to this, health workers are obliged to prescribe antimicrobials (antibacterials) just on the basis of clinical features. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Acute Febrile Illness, Use of Antimicrobial Agents, C-reactive Protein Level
- What is being tested?
- C-reactive Protein Rapid Diagnostic Test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 924 participants
- Where
- 1 siteNepal
- Study dates
- 26 Feb 2023to Dec 2023
- 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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- History of reported fever or fever greater than 100.4◦F (38◦C) with duration of illness up to 7 days
- Duration of fever less than or equal to 7 days
- Can connect with mobile phone for follow up
Who cannot join
- Child younger than 1 year
- Main complaint being trauma or injury
- Symptoms requiring hospital referral
- Impaired consciousness
- Inability to take oral medication
- Convulsions
Show all 13Show fewer
- Confirmed malaria
- Confirmed urinary tract infection
- Local skin infection
- Dental abscess or infection
- Suspicion of tuberculosis
- Any symptom other than fever present for more than 14 days
- Any bleeding such as from skin, nose and gums.
Trial locations and contacts
1 site in 1 country.
Nepal1 site, 1 recruiting
- Recruiting
Paralmi Health Post
Resunga Nagarpalika, Lumbini
Amit Arjyal, MBBS, DPhil, +9779864478329, amitarjyal@pahs.edu.np
About this study
Official title: Rapid Diagnostic Testing for C-reactive Protein to Differentiate Bacterial and Viral Infection in Febrile Patients to Reduce Antimicrobial Use in Remote Health Care Centers of Gulmi District of Nepal: a Cluster Randomized Controlled Trial
In Health Posts of rural areas operated by the Government of Nepal, there are limitations of tests to differentiate between bacterial and viral infections. Due to this, health workers are obliged to prescribe antimicrobials (antibacterials) just on the basis of clinical features. This can lead to irrational use of antimicrobials, consequently contributing to antimicrobial resistance. C-reactive protein is the marker of inflammation which rises during bacterial infection but rarely rises during viral infection. The investigators wish to compare the effect on antimicrobial usage of using CRP(C-Reactive Protein) test, a rapid diagnostic test used to differentiate bacterial and viral infection, with usual standard of care, by carrying out a cluster-randomized controlled trial. The investigators plan to carry out this study in eight Health Posts of Resunga, Dhurkot and Gulmi-Durbar Municipalities of Gulmi District. The investigators will randomly allocate four Health Posts (clusters) to the intervention arm- CRP TESTS in addition to Usual Standard of Care, and four Health Posts (clusters) to the control arm- Usual Standard of Care Alone. The investigators plan to study all patients above one year of age presenting with fever or a history of reported fever with a duration of up to 7 days in Health Posts. Primarily, the investigators will assess the rates of antimicrobial use per patient who presents with febrile illness. Secondarily, the investigators will also assess the outcome of illness of the patient such as need for subsequent hospital admission or severe or complicated illness. This testing method will supplement the existing methods to differentiate bacterial and viral infections based on history and clinical examination by health professionals as a part of usual standard of care in the Health Posts included in this study.
Read the detailed description
The World Health Organization (WHO) defines antimicrobial resistance (AMR) as a situation where drugs used to treat microbial infection caused by bacteria, viruses, fungi and parasites no longer work to treat infection because of the changes in these microbes over time. Though this process of development of AMR is a natural process, it is accelerated by the overuse and misuse of antimicrobials (Mladenovic-Antic et al, 2016, pp.532-537). There were an estimated 1.27 million deaths attributable to bacterial AMR globally in 2019 (Murray et al, 2022). It is estimated that in India every year around sixty thousand newborns die due to AMR (Laxminarayan et al, 2013, pp.1057-1098). As big as the death toll due to AMR is, the economic costs are also significant. Even in a setting of a developed country like the US, direct healthcare cost of AMR is over 6 billion US dollars (CDC, 2019). Nepal is one of the developing countries of the world located in South Asia between India and China. AMR is an increasing problem in Nepal and some of the most common causes for it are excessive use of antimicrobials in animal husbandry and unnecessary use of antimicrobials for treatment of febrile illness (Rijal et al, 2021, pp. 1-14; Acharya and Wilson, 2021, p.105). Currently, bacteria like Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Shigella spp., Vibrio cholera, Neisseria gonorrheae and Staphylococcus aureus are increasingly resistant to the most first-line and some second-line antimicrobials (Acharya and Wilson, 2021 p.105; Basnyat et al, 2015, pp.102-111). Thus antimicrobial resistance (AMR) presents a great threat to public health.
Nepal has its own National Antibiotic Treatment Guideline and according to this even the smallest government healthcare units like health posts can prescribe antimicrobials. These health posts lack microbiology laboratory access and the health worker has to prescribe antimicrobials based upon their history and examination findings which may lead to unnecessary prescription of antimicrobials against viral illness. This challenge of unavailability of laboratory tests can be tackled by introducing point-of-care rapid diagnostic test to detect C-reactive protein to differentiate between bacterial and viral infections. C-reactive protein is the marker of inflammation which rises in blood during bacterial infection but rarely rises during viral infection (Phommasone et al, 2015, pp.1-6). This method has already been used in other developing countries like Laos, Thailand, Myanmar, Malaysia and Vietnam, which have similar socio-economic conditions like that of Nepal (Phommasone et al, 2015, pp.1-6; Althaus et al, 2019, pp.e119-e131; Lubell et al, 2018, pp.1-6; Haenssgen et al, 2018, pp.1-12). Antimicrobials are rarely prescribed based on an absolute certainty of a bacterial infection. The use of point-of-care rapid diagnostic test offers an easy, affordable and a working solution to this problem and helps in judicial use of antimicrobials (O'Neill, 2016). Although it is known that CRP testing can differentiate bacterial and viral infections, the extent to which it can reduce antimicrobial use in a rural health-post setting of Nepal and thus play a role in limiting the emergence of antimicrobial resistance is not known. If this study shows significant reduction in antimicrobial prescription without any adverse clinical outcome, the test kit can be implemented nationally in all low resource health care settings in Nepal.
- Being tested
- C-reactive Protein Rapid Diagnostic Test
- Keywords
- C-Reactive Protein, Acute Febrile Illness, Viral Infection, Bacterial Infection, Antimicrobial Drug, CRP Rapid Test
- Medical subject headings
- Virus Diseases, Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C-reactive Protein Rapid Diagnostic TestDiagnostic test
In the intervention arm in addition to Usual Standard of Care, CRP Testing will be performed. In this test, health worker at health post will prick the finger of the patient using a lancet device following aseptic precautions. A very small drop (10 microliters) of whole blood will be obtained. This will be added to specimen dilution buffer. Then the sample will be mixed by inverting the tube upside down 10-15 times. Then the yellow dip area of the dipstick will be placed into the diluted sample. It will be held there until the liquid rises to the result area by capillary action. The the dipstick is removed from the solution and placed in a horizontal position. The timer will be started and result will be interpreted in 5 minutes. Treatment decision making regarding the use of antimicrobials will be conducted with the help of CRP test results and other clinical features.
| Study group | Role | What they receive |
|---|---|---|
| CRP Tests in addition to Usual Standard of Care | Experimental | For the clusters (health posts) in this arm, the health worker will prick the finger of the eligible patient using a lancet device following aseptic precautions. A very small drop (10 microliters) of whole blood will be obtained which will be added to specimen dilution buffer and the dipstick will be placed into the diluted sample. It will be removed after the liquid rises and the timer will be started and result will be interpreted in 5 minutes. Interpretation of CRP levels: Only red color line (No blue line): <10 mg/L One blue line: 10-40 mg/L Two blue lines: 40-80 mg/L Three blue lines: >80 mg/L. CRP levels of 40 mg/L or above will be considered as increased CRP levels. The decision on antimicrobial use and other treatments will be made with the help of CRP results in addition to information obtained from the history and physical examination. Receives: Diagnostic Test: C-reactive Protein Rapid Diagnostic Test |
| Usual Standard of Care Alone | No intervention | For the clusters (health posts) in this control arm, Usual Standard of Care Alone will be provided. This usual standard of care is given to patients with febrile illness at health posts. Commonly, this involves taking a brief history and conducting a simple physical examination followed by symptomatic treatment such as paracetamol, cough medication or analgesics such as NSAIDs. Often antimicrobial treatment is also prescribed based on clinical suspicion of bacterial infection. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Use of antimicrobial
The investigators will record if the patient was prescribed antimicrobial at the time of presenting to the health post during the current acute febrile illness. This outcome will be recorded as Yes/No
Measured: On the 1 day of recruitment to the study
Secondary outcomes (3)
Complicated Illness
The investigators will record this as outcome of disease after contacting the patient at one month of recruitment and ask whether the patient developed any complications or not. This outcome will be recorded as Complicated Illness (Yes/No). Complicated illness will be defined as need for prolonged course of treatment for more than one week, need to change the initial treatment provided at the health post and give rescue treatment, any severe illness or death. This outcome will be recorded as Yes/No
Measured: One month from recuitment
Referral to hospital
The investigators will record this outcome after contacting the patient at one month of recruitment and ask whether the patient was referred to a hospital. This outcome will be recorded as Yes/No
Measured: One month from recruitment
Admission to hospital
The investigators will record this outcome after contacting the patient at one month of recruitment and ask whether the patient was admitted to hospital. This outcome will be recorded as Yes/No
Measured: One month from recuitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2022
- Study start26 Feb 2023
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Febrile IllnessStudies 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
- Model description
- We will conduct a Cluster Randomized Controlled Trial (cRCT) at eight Health Posts of Gulmi District. Eight Health Posts will be randomly allocated to the intervention arm (use of rapid diagnostic test for C-reactive protein) and the other will be allocated to the control arm. Thus, there will be four Health Posts each in the intervention and control arms.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 924 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Patan Academy of Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Gulmidarbar Rural Municipality, Dhurkot Rural Municipality, Resunga Municipality
- Responsible party
- Principal investigator, Amit Arjyal, Patan Academy of Health Sciences
- Investigators
- Amit Arjyal, MBBS, DPhil, Principal investigator, Patan Academy of Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05292508
- Sponsor's protocol ID
- 1-2022
- Acronym
- CREATIB
- Status last verified
- Jun 2023
- First submitted
- 23 Feb 2022
- Last updated
- 23 Jun 2023
- 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 23 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rapid Diagnostic Testing for C-reactive Protein to Differentiate Bacterial and Viral Infection in Febrile Patients to Reduce Antimicrobial Use in Remote Health Care Centers of Gulmi District of Nepal: a Cluster Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05292508
- Acronym / sponsor ID
- CREATIB / 1-2022
- Keywords
- C-Reactive Protein, Acute Febrile Illness, Viral Infection, Bacterial Infection, Antimicrobial Drug, CRP Rapid Test
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 924 participants (estimated)
- Lead sponsor
- Patan Academy of Health SciencesUniversity, hospital or other
- Collaborators
- Gulmidarbar Rural Municipality, Dhurkot Rural Municipality, Resunga Municipality
- Study start
- 26 Feb 2023 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 23 Mar 2022 (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.
In Health Posts of rural areas operated by the Government of Nepal, there are limitations of tests to differentiate between bacterial and viral infections. Due to this, health workers are obliged to prescribe antimicrobials (antibacterials) just on the basis of clinical features. This can lead to irrational use of antimicrobials, consequently contributing to antimicrobial resistance. C-reactive protein is the marker of inflammation which rises during bacterial infection but rarely rises during viral infection. The investigators wish to compare the effect on antimicrobial usage of using CRP(C-Reactive Protein) test, a rapid diagnostic test used to differentiate bacterial and viral infection, with usual standard of care, by carrying out a cluster-randomized controlled trial. The investigators plan to carry out this study in eight Health Posts of Resunga, Dhurkot and Gulmi-Durbar Municipalities of Gulmi District. The investigators will randomly allocate four Health Posts (clusters) to the intervention arm- CRP TESTS in addition to Usual Standard of Care, and four Health Posts (clusters) to the control arm- Usual Standard of Care Alone. The investigators plan to study all patients above one year of age presenting with fever or a history of reported fever with a duration of up to 7 days in Health Posts. Primarily, the investigators will assess the rates of antimicrobial use per patient who presents with febrile illness. Secondarily, the investigators will also assess the outcome of illness of the patient such as need for subsequent hospital admission or severe or complicated illness. This testing method will supplement the existing methods to differentiate bacterial and viral infections based on history and clinical examination by health professionals as a part of usual standard of care in the Health Posts included in this study.
Detailed description
The World Health Organization (WHO) defines antimicrobial resistance (AMR) as a situation where drugs used to treat microbial infection caused by bacteria, viruses, fungi and parasites no longer work to treat infection because of the changes in these microbes over time. Though this process of development of AMR is a natural process, it is accelerated by the overuse and misuse of antimicrobials (Mladenovic-Antic et al, 2016, pp.532-537). There were an estimated 1.27 million deaths attributable to bacterial AMR globally in 2019 (Murray et al, 2022). It is estimated that in India every year around sixty thousand newborns die due to AMR (Laxminarayan et al, 2013, pp.1057-1098). As big as the death toll due to AMR is, the economic costs are also significant. Even in a setting of a developed country like the US, direct healthcare cost of AMR is over 6 billion US dollars (CDC, 2019). Nepal is one of the developing countries of the world located in South Asia between India and China. AMR is an increasing problem in Nepal and some of the most common causes for it are excessive use of antimicrobials in animal husbandry and unnecessary use of antimicrobials for treatment of febrile illness (Rijal et al, 2021, pp. 1-14; Acharya and Wilson, 2021, p.105). Currently, bacteria like Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Shigella spp., Vibrio cholera, Neisseria gonorrheae and Staphylococcus aureus are increasingly resistant to the most first-line and some second-line antimicrobials (Acharya and Wilson, 2021 p.105; Basnyat et al, 2015, pp.102-111). Thus antimicrobial resistance (AMR) presents a great threat to public health.
Nepal has its own National Antibiotic Treatment Guideline and according to this even the smallest government healthcare units like health posts can prescribe antimicrobials. These health posts lack microbiology laboratory access and the health worker has to prescribe antimicrobials based upon their history and examination findings which may lead to unnecessary prescription of antimicrobials against viral illness. This challenge of unavailability of laboratory tests can be tackled by introducing point-of-care rapid diagnostic test to detect C-reactive protein to differentiate between bacterial and viral infections. C-reactive protein is the marker of inflammation which rises in blood during bacterial infection but rarely rises during viral infection (Phommasone et al, 2015, pp.1-6). This method has already been used in other developing countries like Laos, Thailand, Myanmar, Malaysia and Vietnam, which have similar socio-economic conditions like that of Nepal (Phommasone et al, 2015, pp.1-6; Althaus et al, 2019, pp.e119-e131; Lubell et al, 2018, pp.1-6; Haenssgen et al, 2018, pp.1-12). Antimicrobials are rarely prescribed based on an absolute certainty of a bacterial infection. The use of point-of-care rapid diagnostic test offers an easy, affordable and a working solution to this problem and helps in judicial use of antimicrobials (O'Neill, 2016). Although it is known that CRP testing can differentiate bacterial and viral infections, the extent to which it can reduce antimicrobial use in a rural health-post setting of Nepal and thus play a role in limiting the emergence of antimicrobial resistance is not known. If this study shows significant reduction in antimicrobial prescription without any adverse clinical outcome, the test kit can be implemented nationally in all low resource health care settings in Nepal.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- We will conduct a Cluster Randomized Controlled Trial (cRCT) at eight Health Posts of Gulmi District. Eight Health Posts will be randomly allocated to the intervention arm (use of rapid diagnostic test for C-reactive protein) and the other will be allocated to the control arm. Thus, there will be four Health Posts each in the intervention and control arms.
| Arm | Type | Receives |
|---|---|---|
| CRP Tests in addition to Usual Standard of Care | Experimental | Diagnostic Test: C-reactive Protein Rapid Diagnostic TestFor the clusters (health posts) in this arm, the health worker will prick the finger of the eligible patient using a lancet device following aseptic precautions. A very small drop (10 microliters) of whole blood will be obtained which will be added to specimen dilution buffer and the dipstick will be placed into the diluted sample. It will be removed after the liquid rises and the timer will be started and result will be interpreted in 5 minutes. Interpretation of CRP levels: Only red color line (No blue line): <10 mg/L One blue line: 10-40 mg/L Two blue lines: 40-80 mg/L Three blue lines: >80 mg/L. CRP levels of 40 mg/L or above will be considered as increased CRP levels. The decision on antimicrobial use and other treatments will be made with the help of CRP results in addition to information obtained from the history and physical examination. |
| Usual Standard of Care Alone | No intervention | –For the clusters (health posts) in this control arm, Usual Standard of Care Alone will be provided. This usual standard of care is given to patients with febrile illness at health posts. Commonly, this involves taking a brief history and conducting a simple physical examination followed by symptomatic treatment such as paracetamol, cough medication or analgesics such as NSAIDs. Often antimicrobial treatment is also prescribed based on clinical suspicion of bacterial infection. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- History of reported fever or fever greater than 100.4◦F (38◦C) with duration of illness up to 7 days
- Duration of fever less than or equal to 7 days
- Can connect with mobile phone for follow up
Key exclusion criteria (13 listed)
- Child younger than 1 year
- Main complaint being trauma or injury
- Symptoms requiring hospital referral
- Impaired consciousness
- Inability to take oral medication
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 |
|---|---|---|
| C-reactive Protein Rapid Diagnostic TestIn the intervention arm in addition to Usual Standard of Care, CRP Testing will be performed. In this test, health worker at health post will prick the finger of the patient using a lancet device following aseptic precautions. A very small drop (10 microliters) of whole blood will be obtained. This will be added to specimen dilution buffer. Then the sample will be mixed by inverting the tube upside down 10-15 times. Then the yellow dip area of the dipstick will be placed into the diluted sample. It will be held there until the liquid rises to the result area by capillary action. The the dipstick is removed from the solution and placed in a horizontal position. The timer will be started and result will be interpreted in 5 minutes. Treatment decision making regarding the use of antimicrobials will be conducted with the help of CRP test results and other clinical features. | Diagnostic test | CRP Tests in addition to Usual Standard of Care |
Primary outcome
Use of antimicrobial
Time frame: On the 1 day of recruitment to the study
The investigators will record if the patient was prescribed antimicrobial at the time of presenting to the health post during the current acute febrile illness. This outcome will be recorded as Yes/No
3 secondary outcomes
Complicated Illness
Time frame: One month from recuitment
Referral to hospital
Time frame: One month from recruitment
Admission to hospital
Time frame: One month from recuitment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2023.
- 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.
Amit Arjyal, MBBS, DPhil principal investigator
Patan Academy of Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing C-reactive Protein Rapid Diagnostic Test in people with Acute Febrile Illness and Use of Antimicrobial Agents, run by Patan Academy of Health Sciences at 1 site in Nepal.
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 13 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: status not confirmed, as of the sponsor's last update on 23 Jun 2023. 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 Nepal. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Amit Arjyal, MBBS, DPhil (+9779864478329, amitarjyal@pahs.edu.np), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Use of antimicrobial (time frame: On the 1 day of recruitment to the study). 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 23 Jun 2023.