Phase IV, randomized, open label, parallel groups clinical trial for evaluating the early Stop of antibiotic Treatment in high-risk febrile neutropenic Oncohaematological Paediatric patients (e-STOP 2)

2025-524264-38-00 Protocol AB.OH.2025 Therapeutic use (Phase IV) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 4 sites · Protocol AB.OH.2025

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Authorised, recruitment pending
Participants planned 136
Countries 1
Sites 4

Infectious diseases

To evaluate the safety of discontinuing antibiotic therapy in paediatric patients with cancer and FN without proven invasive bacterial infection (IBI), who show good clinical evolution (resolution of fever and clinical stability), low biomarker levels (CRP <5 mg/dL or CRP <9 mg/dL and PCT <0.5 ng/mL), and an ANC <500/m…

Key facts

Sponsor
Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca
Participant type
Pediatric, Patients
Age range
0-17 years, 18-64 years
Gender
Male and Female
Therapeutic area
Not possible to specify
Decision date (initial)
2026-05-05
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the safety of discontinuing antibiotic therapy in paediatric patients with cancer and FN without proven invasive bacterial infection (IBI), who show good clinical evolution (resolution of fever and clinical stability), low biomarker levels (CRP <5 mg/dL or CRP <9 mg/dL and PCT <0.5 ng/mL), and an ANC <500/mm³ at 48–72 hours after the FN episode. The proportion of episodes of febrile neutropenia with uncomplicated resolution at 28 days from the onset of the episode will be compared.
Uncomplicated resolution will be defined as the absence of:
-death from any cause
-admission to the ICU
-sepsis
-microbiologically documented bacterial infection
-clinically documented bacterial infection (including radiologically confirmed pneumonia)

Secondary objectives 4

  1. To evaluate the efficacy of this strategy by assessing the reduction in the number of days of antibiotic therapy in the experimental group. The number of antibiotic days will be compared between both groups to confirm that it is significantly lower in the experimental group.
  2. To evaluate the reduction in adverse effects associated with prolonged antibiotic therapy in the experimental group. Antibiotic-related adverse events will be compared between both groups to confirm that they are significantly lower in the experimental group.
  3. To retrospectively evaluate the usefulness of biomarkers (CRP, PCT and IL-8) for improved prediction of invasive bacterial infection (IBI).
  4. To validate an IBI prediction system in this population.

Conditions and MedDRA coding

Infectious diseases

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

  1. Male and female patients ≤18 years of age expected to develop prolonged neutropenia (>7 days), with: • Acute myeloblastic leukaemia at any phase of chemotherapy • Acute lymphoblastic leukaemia in induction, consolidation, or intensification phases • Biphenotypic leukaemia at any phase of chemotherapy • Lymphoblastic lymphoma in induction and consolidation phases • B-cell receiving high-intensity chemotherapy • Anaplastic lymphoma receiving high-intensity chemotherapy • Solid tumours receiving high-intensity chemotherapy • Relapsed leukaemia at any phase of treatment
  2. Episode of febrile neutropenia (FN), defined as a single axillary temperature ≥38.0°C in a patient with an absolute neutrophil count (ANC) <500 neutrophils/mm³, or expected to fall below this value within the next 48–72 hours
  3. Antibiotic treatment initiated for the current FN episode (routine antimicrobial prophylaxis is allowed, as well as teicoplanin 3 days/week for patients with AML included in the CHIP-AML-2022 protocol and therefore in the Pro-teico study).
  4. Low risk of invasive bacterial infection (IBI) at the start of the FN episode. Patients must meet all of the following: • CRP <9 mg/dL • PCT <0.5 ng/mL • Absence of hypotension
  5. Absence of proven or clinically suspected bacterial infection 48–72 hours after the FN episode. This includes: • No bacterial microbiological isolation from relevant clinical samples. • No signs, symptoms, or clinical or radiological findings suggestive of a localised or invasive infection. In cases where a microbiological isolate is considered a contaminant, the patient may still be considered for inclusion provided that: • The isolated microorganism is consistent with contamination according to standard microbiological criteria. • There are no clinical, laboratory, or radiological signs suggestive of bacterial infection
  6. Good clinical evolution 48–72 hours after the FN episode, defined as: • Afebrile for >48 hours (axillary temperature <38°C) • Haemodynamically stable • Stable paediatric early warning score (PEWS)
  7. CRP <5 mg/dL, or CRP <9 mg/dL and PCT <0.5 ng/mL, with decreasing trend at the time of randomisation (values will be assessed on day 3 and day 5 after the FN episode).
  8. ANC <500 neutrophils/mm³ at the time of randomisation.
  9. Signed informed consent from the patient and/or parent(s)/legal representative(s).
  10. Patient and/or parent(s)/legal representative(s) must have sufficient reading and writing skills to understand and provide consent to participate in the study
  11. Patient and/or parent(s)/legal representative(s) must be considered reliable and capable of adhering to the protocol.

Exclusion criteria 7

  1. Antibiotic treatment at the time of the FN episode different from that used prophylactically.
  2. Empirical antibiotic treatment different from that recommended in international guidelines
  3. Patient with poor clinical evolution during the first 12 hours (hemodynamic instability, PICU admission, death).
  4. Active participation in the same study at the onset of the current FN episode.
  5. Active participation in another clinical trial that, in the investigators’ opinion, may interfere with the assessment of the results.
  6. Any condition which, in the investigator’s opinion, makes study participation unsuitable for the patient or could limit, prevent, or confound the assessments planned in the protocol.
  7. Female patients who are pregnant or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. To evaluate the safety of discontinuing antibiotics by comparing the proportion of febrile neutropenia episodes with uncomplicated resolution at 28 days between the experimental group and the control group.

Secondary endpoints 11

  1. Days with fever.
  2. Days and type of antimicrobials administered.
  3. Days of neutropenia.
  4. Patient characteristics: age, sex, underlying disease, treatment phase, days since last chemotherapy cycle, type of catheter, clinical characteristics, physical examination, hours of fever on admission, vital signs, admission to paediatric ICU, risk stratification
  5. Laboratory values (at the start of the FN episode, at 48-72 hours, at 5 days - if applicable - and at 28 days): complete blood count, serum biochemistry (see Appendix II), CRP, PCT.
  6. IL-8 (at the onset of NF and at 48-72 hours)
  7. Microbiological results: blood cultures and urine cultures and others if performed (nasopharyngeal swab, cerebrospinal fluid culture, etc.).
  8. Results of B-HCG in urine.
  9. Imaging test results: X-ray, CT, MRI, ultrasound, among others.
  10. Incidence and severity of adverse events
  11. Concomitant medication

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 16

Metronidazole

SUB08922MIG · Substance

Active substance
Metronidazole
Pharmaceutical form
FILM COATED TABLET
Route of administration
ORAL
Max daily dose
30 mg/Kg milligram(s)/kilogram
Max total dose
2.25 g gram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Meropenem

SUB08778MIG · Substance

Active substance
Meropenem
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
120 mg/kg milligram(s)/kilogram
Max total dose
6 g gram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Piperacillin

SUB09867MIG · Substance

Active substance
Piperacillin
Pharmaceutical form
POWDER FOR SOLUTION FOR INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
400 mg/kg milligram(s)/kilogram
Max total dose
16 g gram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ciprofloxacin

SUB07470MIG · Substance

Active substance
Ciprofloxacin
Pharmaceutical form
FILM COATED TABLET
Route of administration
ORAL
Max daily dose
40 mg/kg milligram(s)/kilogram
Max total dose
1.5 g gram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Levofloxacin

SUB08471MIG · Substance

Active substance
Levofloxacin
Pharmaceutical form
FILM COATED TABLET
Route of administration
ORAL
Max daily dose
20 mg/kg milligram(s)/kilogram
Max total dose
750 mg milligram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Vancomycin

SUB05076MIG · Substance

Active substance
Vancomycin
Pharmaceutical form
POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION AND FOR ORAL SOLUTION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
60 mg/Kg milligram(s)/kilogram
Max total dose
4 g gram(s)
Max treatment duration
28 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Metronidazole

SUB08922MIG · Substance

Active substance
Metronidazole
Pharmaceutical form
ORAL SUSPENSION
Route of administration
ORAL
Max daily dose
30 mg/kg milligram(s)/kilogram
Max total dose
2.25 g gram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ciprofloxacin

SUB07470MIG · Substance

Active substance
Ciprofloxacin
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
30 mg/Kg milligram(s)/kilogram
Max total dose
1.2 g gram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ciprofloxacin

SUB07470MIG · Substance

Active substance
Ciprofloxacin
Pharmaceutical form
ORAL SUSPENSION
Route of administration
ORAL
Max daily dose
40 mg/Kg milligram(s)/kilogram
Max total dose
1.5 g gram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ceftazidime

SUB07422MIG · Substance

Active substance
Ceftazidime
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION OR INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
150 mg/kg milligram(s)/kilogram
Max total dose
8 g gram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Cefepime

SUB07390MIG · Substance

Active substance
Cefepime
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
150 mg/kg milligram(s)/kilogram
Max total dose
6 g gram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Metronidazole

SUB08922MIG · Substance

Active substance
Metronidazole
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
30 mg/kg milligram(s)/kilogram
Max total dose
4 g gram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Levofloxacin

SUB08471MIG · Substance

Active substance
Levofloxacin
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
20 mg/Kg milligram(s)/kilogram
Max total dose
750 mg milligram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Tazobactam

SUB10849MIG · Substance

Active substance
Tazobactam
Pharmaceutical form
POWDER FOR SOLUTION FOR INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
37.5 mg/kg milligram(s)/kilogram
Max total dose
2.25 g gram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Amikacin

SUB05431MIG · Substance

Active substance
Amikacin
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
22.5 mg/Kg milligram(s)/kilogram
Max total dose
1.5 g gram(s)
Max treatment duration
10 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Teicoplanin

SUB04714MIG · Substance

Active substance
Teicoplanin
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INFUSIÓN INTRAVENOSA
Max daily dose
12 mg/Kg milligram(s)/kilogram
Max total dose
800 g gram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

18 Total trials 7 Recruiting 3 Ended
Academic / Non-commercial
Sponsor organisation
Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca
Address
Passeig De La Vall D'Hebron 119-129
City
Barcelona
Postcode
08035
Country
Spain

Scientific contact point

Organisation
Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca
Contact name
Natalia Mendoza Palomar

Public contact point

Organisation
Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca
Contact name
Natalia Mendoza Palomar

Locations

1 EU/EEA country · 4 investigational sites

By country

CountryMS statusPlanned subjectsSites
Spain Authorised, recruitment pending 136 4
Rest of world — 0 —

Investigational sites

Spain

4 sites · Authorised, recruitment pending
Hospital Universitario La Paz
Infectious diseases, Paseo De La Castellana 261, 28046, Madrid
Hospital Infantil Universitario Nino Jesus
Infectious diseases, Avenida De Menendez Pelayo 65, 28009, Madrid
Hospital Sant Joan De Deu Barcelona
Infectious diseases, Passeig De Sant Joan De Deu 2, 08950, Esplugues De Llobregat
Hospital Universitari Vall D Hebron
Infectious diseases, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 49 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol Spanish_EU-CT_2025-524264-38-00 1.0
Protocol (for publication) D1_Protocol Spanish_EU-CT_2025-524264-38-00_ clean 1.0
Protocol (for publication) D1_Protocol Spanish_EU-CT_2025-524264-38-00_cambios 1.0
Recruitment arrangements (for publication) K1_Recruitment arrangements_EU-CT_2025-524264-38-00 1
Subject information and informed consent form (for publication) L1_SIS and ICF Hoja Informativa Padres 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Hoja Informativa Padres_cambios 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Hoja Informativa Padres_limpio 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Menores_12-17 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Menores_12-17_cambios 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Menores_12-17_limpio 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Representante legal-Progenitores 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Representante legal-Progenitores_ cambios 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Representante legal-Progenitores_clean 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Adultos 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Adultos_cambios 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF_Adultos_clean 1.0
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC _71286_PiperacilinaTazobactam 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC _71286_PiperacilinaTazobactam 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC _71286_PiperacilinaTazobactam 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_35034_Metronidazol comprimidos 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_35034_Metronidazol comprimidos 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_47656_Metronidazol suspension 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_47656_Metronidazol suspension 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_62485_Ciprofloxacino_comprimidos 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_62485_Ciprofloxacino_comprimidos 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_62602_Ciprofloxacino_suspension 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_62602_Ciprofloxacino_suspension 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_63879_Amikacina_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_63879_Amikacina_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_67554_Ciprofloxacino perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_67554_Ciprofloxacino perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_68091_Metronidazol_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_68091_Metronidazol_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_68867_Levofloxacino_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_68867_Levofloxacino_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_72674_Ceftazidima_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_72674_Ceftazidima_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_72750_Cefepima_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_72750_Cefepima_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_83988_Meropenem_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_85651_Vancomicina_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_85651_Vancomicina_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_85874_Teicoplanina_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_85874_Teicoplanina_perfusion 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC75614_Levofloxacino oral 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC75614_Levofloxacino oral 1
Synopsis of the protocol (for publication) D1_Protocol Synopsis_EU-CT_2025-524264-38-00 1.0
Synopsis of the protocol (for publication) D1_Protocol Synopsis_EU-CT_2025-524264-38-00_cambios 1.0
Synopsis of the protocol (for publication) D1_Protocol Synopsis_EU-CT_2025-524264-38-00_clean 1.0

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2026-01-28 Spain Acceptable
2026-04-30
 2026-05-05

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