Clinical trial NCT04081051: Advancing Access to Diagnostic Innovation Essential for UHC and AMR Prevention
Official title: Impact of Improved Diagnostic Tools, Training and Communication on Acute Fever Case Management and Antibiotic Prescriptions for Children and Adolescents Presenting at Outpatient Facilities in Lower & Middle-Income Countries.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Febrile Illness
Lead sponsor: Foundation for Innovative New Diagnostics, Switzerland
Sponsor class: OTHER
Collaborators: name: University of Oxford
name: Indian Council of Medical Research
name: WHO, Special Programme for Research and Training in Tropical Diseases (TDR)
First posted: 2019-09-06
Enrollment: 17294
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This study aims to evaluate clinical outcomes and antibiotic prescription patterns following the use of diagnostic algorithms, point of care (PoC) rapid diagnostic tests, and behaviour change interventions in cases of acute febrile illnesses in children, adolescents and adults presenting at out patient clinics in lower and middle income countries. The study is to be implemented in 2 phases- the first run from 2020 to 2021 and the 2nd phase from 2021 to 2022 to include COVID-19 PoCTs.

Detailed description: Background and rationale. 'Just-in-case' antibiotic prescribing practices is one of the causes of inadequate management of 'acute febrile illnesses' and AMR in Low- and Middle-income Countries (LMICs). At the same time, some people who would require antibiotic treatment do not get it. An improvement in case management and prescription practice might lead to a decrease in morbidity and mortality. Success will mean making significant steps toward achieving the dual goal of improving UHC and tackling AMR.

The PICO question addressed is: in children/ adolescents and adults (Population) presenting to outpatient clinics / peripheral health centres in LMICs with acute febrile illness/Respiratory Tract Infection can a combination of available PoC rapid diagnostic tests, diagnostic aids/algorithms, clinic process flow and, training and communication (Intervention) improve management of acute febrile illnesses and better target the use of antibiotics / reduce unnecessary antibiotic prescriptions (Outcomes) compared to current practice (Control)?

Primary objective(s).

To evaluate the impact of a package of interventions (point of care \[PoC\] tests, clinical algorithm, clinic process flow, training and communication tools) on clinical outcomes and antibiotic prescriptions, with standard-of-care practices, in children and adolescents presenting with acute febrile illnesses (defined as fever with no focus or Respiratory Tract Infection lasting for no more than 7 days), at outpatient clinics.

Secondary objective(s)

1. To improve the management of acute febrile illness
2. To promote rational and targeted use of antibiotics for acute febrile illness
3. To determine the aetiology of fever in patients presenting to outpatient facilities using available PoC diagnostic tests
4. To study the safety and feasibility of a package of interventions compared to current practice of care
5. To assess the effectiveness of training and communication tools to adherence to the prescribed treatment

Primary endpoints

1. Proportion of outpatient cases of acute febrile illness with favourable outcome (defined as being alive and asymptomatic).
2. antibiotic prescriptions rates for acute febrile illness in the clinic Secondary endpoints (outcomes) 1. Duration of time spent in the clinic

2. Proportion of patients treated for specific bacterial infection 3. Proportion of patients with disease specific diagnosis identified by PoC tests 4. Frequency of serious adverse event (SAE) within 7 days of recruitment 5. Frequency of unscheduled (unplanned) visit within 7 days of recruitment 6. Training and communication package uptake 7. Proportion of patients prescribed antibiotic at clinic who reported adherence to prescription on day 7 8. Proportion of patients who were not prescribed antibiotics at clinic who received antibiotics elsewhere between day 0 and day 7 9. Behaviour Change Intervention Recommendations

Trial design: A multi-centre, open label, two arm, randomized-controlled trial

Trial sites: This study will be conducted in outpatient departments and primary care clinics in Burkina Faso, Ghana, India, Nepal and Uganda.

Trial population: The study population will consist of children, adolescents and adults presenting to the health care facility, or provider, with acute fever or history of fever

Sample Size: 19,922

Eligibility criteria: Inclusion Criteria:

* Patients presenting with fever with no focus/RTI:

  * Children (6 months to \<12 years) and adolescents (12 years to less than 18 years old) of both sexes .
  * Presenting with an acute febrile illness defined as temperature of \>37.5°C or history of fever within the last 7 days with no focus or suspected RTI.
  * Parent/guardian providing written informed consent for their children if less than 18 years of age.
  * Obtain assent for adolescent between 12 and less than 18 years old
  * Willing to provide blood and other samples and adhere to study procedures explained in the consent forms following the protocol.
  * Available and willing to return for follow-up visit at the health facility on day 7 (+/- 2 days).

Exclusion Criteria:

* o Children and adolescents from 6 months to less than 18 years old presenting with chronic febrile illness (fever lasting more than 7 days).

  * Patients with acute febrile illness outside the allowed age range for the site.
  * Severely ill patients requiring hospital admission or referral as assessed by the study clinicians.
  * Anyone refusing consent to the study or not able to attend the health centre for follow-up (adults, the children of parents/guardians, or adolescents who refuse or are missed when asking for consent).

Primary outcomes:
measure: Proportion of acute febrile cases with favorable clinical outcomes at day 7
timeFrame: Day 7
measure: Antibiotic prescription rates in acute fever cases
timeFrame: Day 0
Secondary outcomes:
measure: Proportion of participants with acute fever Diagnoses identified by point of care tests.
timeFrame: Day 0
measure: Adverse events
timeFrame: Day 7
measure: Time spent in the clinic
timeFrame: Day 0
measure: Proportion of study participants who adhered to antibiotic prescriptions
timeFrame: Day 7
Other outcomes:
Locations:
city: Nanoro
country: Burkina Faso
facility: IRSS-DRCO/Clinical Research Unit of Nanoro (CRUN)
city: Accra
country: Ghana
facility: Shai-Osudoku District Hospital
state: Dodowa
city: Ganiyari
country: India
facility: Jan Swathya Sahyog
state: Chhattisgarh
city: Beliaghata
country: India
facility: National Institute of Cholera & Enteric Diseases
state: Kolkata
city: Ujjain
country: India
facility: R D Gardi Medical College
state: Madhya Pradesh
city: Chandigarh
country: India
facility: Post Graduate Insitute Medical Education and Research
city: Lalitpur
country: Nepal
facility: Patan Academy of Health Sciences
state: Lagankhel
city: Kampala
country: Uganda
facility: Infectious Disease research collaboration
Study officials:
affiliation: Foundation for Innovative New Diagnostics (FIND)
name: Piero Olliaro, MD
role: STUDY_DIRECTOR
References:
citation: Salami O, Horgan P, Moore CE, Giri A, Sserwanga A, Pathak A, Basnyat B, Kiemde F, Smithuis F, Kitutu F, Phutke G, Tinto H, Hopkins H, Kapisi J, Swe MMM, Taneja N, Baiden R, Dutta S, Compaore A, Kaawa-Mafigiri D, Hussein R, Shakya SU, Kukula V, Ongarello S, Tomar A, Chadha SS, Walia K, Kelly-Cirino C, Olliaro P. Impact of a package of diagnostic tools, clinical algorithm, and training and communication on outpatient acute fever case management in low- and middle-income countries: protocol for a randomized controlled trial. Trials. 2020 Nov 25;21(1):974. doi: 10.1186/s13063-020-04897-9.