Trial Outcomes & Findings for Personalised Risk Assessment in Febrile Illness to Optimise Real-life Management Across the European Union (PERFORM) (NCT NCT03502993)

NCT ID: NCT03502993

Last Updated: 2023-10-13

Results Overview

Clinically-assigned retrospective phenotype, according to the cause of illness

Recruitment status

COMPLETED

Target enrollment

7247 participants

Primary outcome timeframe

Participants were monitored for outcome throughout their stay in hospital, and received follow-up review at 10 days

Results posted on

2023-10-13

Participant Flow

Participant milestones

Participant milestones
Measure
BIVA Studies
A minimum of 3,000 children will be recruited to the BIVA-ED study, in order to capture sufficient children with confirmed bacterial infection. Additional children with less common febrile illnesses will also be recruited: 500 critically ill (BIVA-PIC); 200 at high-risk of bacterial illness through primary or secondary immunodeficiency (BIVA-HR); 150 with an inflammatory diagnosis, whose initial presentation is difficult to discriminate from bacterial infection (BIVA-INF). Samples collected from recruits in the BIVA studies will be used for the validation of biomarkers (clinical, proteomic and transcriptomic biomarkers) for diagnosis of febrile illness, including markers of bacterial and viral infection (confirmed by culture and/or molecular microbiology) and inflammatory conditions. Validation of biomarker
Control Children Without Fever or Suspicion of Infection
Children attending hospital for reasons other than for investigation of febrile illness or suspicion of infection
Overall Study
STARTED
5957
1290
Overall Study
COMPLETED
5957
1290
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Participants excluded from age analysis if data missing or incomplete

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
BIVA Studies
n=5957 Participants
A minimum of 3,000 children will be recruited to the BIVA-ED study, in order to capture sufficient children with confirmed bacterial infection. Additional children with less common febrile illnesses will also be recruited: 500 critically ill (BIVA-PIC); 200 at high-risk of bacterial illness through primary or secondary immunodeficiency (BIVA-HR); 150 with an inflammatory diagnosis, whose initial presentation is difficult to discriminate from bacterial infection (BIVA-INF). Samples collected from recruits in the BIVA studies will be used for the validation of biomarkers (clinical, proteomic and transcriptomic biomarkers) for diagnosis of febrile illness, including markers of bacterial and viral infection (confirmed by culture and/or molecular microbiology) and inflammatory conditions. Validation of biomarker
Controls for BIVA Studies
n=1290 Participants
Age-matched control patients will not have had a febrile illness, major trauma or vaccination within the previous three weeks and who are having routine blood sampling for reasons other than investigation of infectious or inflammatory disease. Control children may include critically ill children without infection or those with healthcare associated infections. Where data was incomplete, patients were not included in the analysis - therefore the number analysed is not always 1290
Total
n=7247 Participants
Total of all reporting groups
Age, Customized
age on presentation
4.57 years
n=5924 Participants • Participants excluded from age analysis if data missing or incomplete
9.64 years
n=1231 Participants • Participants excluded from age analysis if data missing or incomplete
5.32 years
n=7155 Participants • Participants excluded from age analysis if data missing or incomplete
Sex: Female, Male
Female
2638 Participants
n=5957 Participants • Participants excluded from sex analysis if data missing or incomplete
544 Participants
n=1239 Participants • Participants excluded from sex analysis if data missing or incomplete
3182 Participants
n=7196 Participants • Participants excluded from sex analysis if data missing or incomplete
Sex: Female, Male
Male
3319 Participants
n=5957 Participants • Participants excluded from sex analysis if data missing or incomplete
695 Participants
n=1239 Participants • Participants excluded from sex analysis if data missing or incomplete
4014 Participants
n=7196 Participants • Participants excluded from sex analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · North/Mid/East European
2999 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
718 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
3717 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · South European
1209 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
384 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
1593 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Mandinka
194 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
0 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
194 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · unknown
146 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
0 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
146 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Roma European
115 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
2 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
117 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Mixed
110 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
17 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
127 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · FULA
97 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
0 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
97 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Gambian
93 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
0 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
93 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Arabian Peninsula/Arab Middle East
91 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
9 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
100 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · West Asian
88 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
11 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
99 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · WOLOF
70 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
0 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
70 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · North African
67 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
7 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
74 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · East Asian
61 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
21 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
82 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · other
46 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
9 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
55 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Serahule
45 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
0 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
45 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Afro-Carribean
31 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
5 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
36 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · South East Asian
30 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
1 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
31 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Native South American
18 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
3 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
21 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Other African
13 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
10 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
23 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Other EU
8 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
1 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
9 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Other Asian
3 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
3 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
6 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · South Asian Nepal
3 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
0 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
3 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Jewish
7 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
0 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
7 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · South Asian Indian, Pakistani, Bangladeshi
170 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
20 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
190 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Subsaharan Africa
112 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
9 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
121 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Race/Ethnicity, Customized
reported ethnicity/race · Turkish
44 Participants
n=5870 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
7 Participants
n=1237 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
51 Participants
n=7107 Participants • Participants excluded from race/ethnicity analysis if data missing or incomplete
Co-morbidities leading to increased infection risk, BIVA studies
446 participants
n=5957 Participants • Participants excluded from Co-morbidities leading to increased infection risk, BIVA studies analysis if data missing or incomplete
43 participants
n=1250 Participants • Participants excluded from Co-morbidities leading to increased infection risk, BIVA studies analysis if data missing or incomplete
489 participants
n=7207 Participants • Participants excluded from Co-morbidities leading to increased infection risk, BIVA studies analysis if data missing or incomplete

PRIMARY outcome

Timeframe: Participants were monitored for outcome throughout their stay in hospital, and received follow-up review at 10 days

Population: Number of children with definite bacterial illness assessed by positive blood culture and/or positive culture of sample from sterile site

Clinically-assigned retrospective phenotype, according to the cause of illness

Outcome measures

Outcome measures
Measure
BIVA Studies
n=5952 Participants
A minimum of 3,000 children will be recruited to the BIVA-ED study, in order to capture sufficient children with confirmed bacterial infection. Additional children with less common febrile illnesses will also be recruited: 500 critically ill (BIVA-PIC); 200 at high-risk of bacterial illness through primary or secondary immunodeficiency (BIVA-HR); 150 with an inflammatory diagnosis, whose initial presentation is difficult to discriminate from bacterial infection (BIVA-INF). Samples collected from recruits in the BIVA studies will be used for the validation of biomarkers (clinical, proteomic and transcriptomic biomarkers) for diagnosis of febrile illness, including markers of bacterial and viral infection (confirmed by culture and/or molecular microbiology) and inflammatory conditions. Validation of biomarker
Controls for BIVA Studies
n=1290 Participants
Age-matched control patients will not have had a febrile illness, major trauma or vaccination within the previous three weeks and who are having routine blood sampling for reasons other than investigation of infectious or inflammatory disease. Control children may include critically ill children without infection or those with healthcare associated infections. Where data was incomplete, patients were not included in the analysis - therefore the number analysed is not always 1290
Number of Participants With Clinically-assigned Retrospective Phenotype
655 Participants
0 Participants

Adverse Events

BIVA Studies

Serious events: 120 serious events
Other events: 0 other events
Deaths: 50 deaths

Healthy Controls

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
BIVA Studies
n=5957 participants at risk
A minimum of 3,000 children will be recruited to the BIVA-ED study, in order to capture sufficient children with confirmed bacterial infection. Additional children with less common febrile illnesses will also be recruited: 500 critically ill (BIVA-PIC); 200 at high-risk of bacterial illness through primary or secondary immunodeficiency (BIVA-HR); 150 with an inflammatory diagnosis, whose initial presentation is difficult to discriminate from bacterial infection (BIVA-INF). Samples collected from recruits in the BIVA studies will be used for the validation of biomarkers (clinical, proteomic and transcriptomic biomarkers) for diagnosis of febrile illness, including markers of bacterial and viral infection (confirmed by culture and/or molecular microbiology) and inflammatory conditions. Validation of biomarker
Healthy Controls
n=1290 participants at risk
Children attending hospital for reasons other than investigation of febrile illness or suspicion of infection
Blood and lymphatic system disorders
Sepsis syndrome
2.0%
120/5957 • Number of events 120 • Participants were monitored for adverse outcomes throughout their stay in hospital and monitored upto follow up period of 10 days
Observational study; outcome (death)
0.00%
0/1290 • Participants were monitored for adverse outcomes throughout their stay in hospital and monitored upto follow up period of 10 days
Observational study; outcome (death)

Other adverse events

Adverse event data not reported

Additional Information

Dr J Herberg

Imperial College London

Phone: 0207 594 3900

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place