Title

Impact of improved diagnostic tools, practices, training and communication on acute fever case management and antibiotic prescriptions for children and adolescents presenting at outpatient facilities of Jan Swasthya Sahyog, India.

Short title

Advancing access to diagnostic innovation essential for AMR prevention

Protocol version and date

AM001 version 0.2

1^st October 2019

Background and rationale

A ‘just-in-case’ antibiotics prescription practice is one of the causes of both antimicrobial resistance (AMR) and inadequate management of acute febrile illnesses, both resulting in increased morbidity and mortality. At the same time, many patients who would require antibiotic treatment do not get it. An adaptation in current practice needs to occur to improve case management in India. Success will mean making significant steps toward achieving the goal of tackling AMR.

The PICO question addressed is:

â–ª          In children and adolescents presenting to outpatient clinics / peripheral health centres in India with acute febrile illness / Respiratory Tract Infection (Population),

â–ª          by combining available diagnostic tests plus algorithms plus clinic process flow plus training and communication for care-givers and users (Intervention)

â–ª          over current practice (Control)

â–ª          can we improve patients management of acute febrile illnesses and better target the use of antibiotics / reduce unnecessary antibiotic prescriptions as appropriate and feasible (Outcome)?

Primary objective(s)

To compare the impact of a package of interventions (diagnostic tests plus algorithms plus clinic process flow plus training and communication for care-givers and users) 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 in India.

Secondary objective(s)

1.    To assess the adherence to new practices by health care workers and patients/caregivers

2.    To study the safety and feasibility of a package of interventions compared to current practice of care.

Primary endpoints

(outcomes)

1.    Proportion of outpatient cases of acute febrile illness with favourable outcome (defined as being alive and asymptomatic)

2.    Rates of antibiotic prescriptions for acute febrile illness in the clinic

Secondary endpoints (outcomes)

·         Adherence to new algorithm by health care workers

·         Adherence to prescription by patients/caregivers.

·         Rates of adverse events

Trial design

Prospective, open label, randomised, controlled trial

Trial sites/setting

The study will be conducted in 4 sites namely: JSS Hospital, Bahmni HWC, Shivtarai HWC, Semariya HWC

Trial population

The study population will consist of children (6 months to <12years) and adolescents (12 to <18 years old) presenting to the health care facility, with current or history (within last 7 days)  of acute febrile illness or suspected respiratory tract infection

Sample Size

864 in each arm. 1728 total

Eligibility criteria

o   Inclusion Criteria

o    

o   Patients with fever with no focus / respiratory tract infection:

o   Children (6 months to <12years) and adolescents (12 to <18 years old)

o   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 Respiratory Tract Infection

o   Parent/guardian providing written informed consent for their children if <18 years.

o   Assent for adolescents between 12 and <18 years.

o   Willing to provide blood samples and adhere to study procedures explained in the consent forms following the protocol.

o   Available and willing to return for follow-up visit at the health facility.

Exclusion Criteria

Participants are excluded using the following exclusion criteria:

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

o   Patients with acute febrile illness outside the allowed age range.

o   Severely ill patients requiring hospital admission or referral as assessed by the study clinicians.

o   Anyone refusing consent to be part of the study or not available for follow-up (adults, the parents/guardians of children, or adolescents who refuse or are missed when asking for consent).

Trial duration

18 months overall, including 6 months of baseline study and 12 months of intervention and patient recruitment. Total follow-up duration per enrolled patient is 7 (+/-2) days.

Time schedule

Protocol development – September 2019

Approvals – Sep - Dec 2019

Social science research first phase- 4.5 months (Jan – mid May)

Clinical Enrolment starts Mid May 2020

Enrolment ends Mid May 2021

Study ends June 2021