## Protocol Section
### Identification Module
**NCT ID:** NCT06426836

**Acronym:** PADECMO

**Brief Title:** Pediatric Antibiotic Dosing in Extracorporal Membrane Oxygenation (PADECMO)

**Official Title:** Pediatric Antibiotic Dosing in Extracorporal Membrane Oxygenation

#### Organization Study ID Info
**ID:** EC 2015/0529
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Ghent
### Status Module
#### Completion Date
**Date:** 2026-07-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-23

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-17

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-12-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2016-08-19

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-23
**Type:** ACTUAL
**Study First Submit Date:** 2022-05-13
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Ghent

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Pharmacokinetics of antibiotics in critically ill neonates, infants and children on extracorporeal membrane oxygenation (ECMO).

**Detailed Description:** The study will investigate whether - with the current dosing regimens of meropenem, piperacillin-tazobactam, amoxicillin-clavulanate, cephazolin, vancomycin, amikacin, teicoplanin and ciprofloxacin - pharmacodynamic targets are attained in a national multicentric clinical setting in pediatric patients on ECMO.

### Conditions Module

**Conditions:**

- Pharmacokinetics

- Amoxicillin-clavulanate

- Piperacillin-tazobactam

- Meropenem

- Cefazolin

- Teicoplanin

- Vancomycin

- Ciprofloxacin

- Amikacin

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** OTHER

#### Enrollment Info

**Count:** 300

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients receiving amoxicillin-clavulanate as part of routine clinical care. Study procedure: blood sampling

**Intervention Names:**

- Other: Amoxicillin-clavulanate

**Label:** Amoxicillin-clavulanate

**Type:** OTHER

#### Arm Group 2

**Description:** Patients receiving piperacillin-tazobactam as part of routine clinical care. Study procedure: blood sampling

**Intervention Names:**

- Other: Piperacillin-tazobactam

**Label:** Piperacillin-tazobactam

**Type:** OTHER

#### Arm Group 3

**Description:** Patients receiving meropenem as part of routine clinical care. Study procedure: blood sampling

**Intervention Names:**

- Other: Meropenem

**Label:** Meropenem

**Type:** OTHER

#### Arm Group 4

**Description:** Patients receiving cefazolin as part of routine clinical care. Study procedure: blood sampling

**Intervention Names:**

- Other: Cefazolin

**Label:** Cefazolin

**Type:** OTHER

#### Arm Group 5

**Description:** Patients receiving vancomycin as part of routine clinical care. Study procedure: blood sampling

**Intervention Names:**

- Other: Vancomycin

**Label:** Vancomycin

**Type:** OTHER

#### Arm Group 6

**Description:** Patients receiving teicoplanin as part of routine clinical care. Study procedure: blood sampling

**Intervention Names:**

- Other: Teicoplanin

**Label:** Teicoplanin

**Type:** OTHER

#### Arm Group 7

**Description:** Patients receiving ciprofloxacin as part of routine clinical care. Study procedure: blood sampling

**Intervention Names:**

- Other: Ciprofloxacin

**Label:** Ciprofloxacin

**Type:** OTHER

#### Arm Group 8

**Description:** Patients receiving amikacin as part of routine clinical care. Study procedure: blood sampling

**Intervention Names:**

- Other: Amikacin

**Label:** Amikacin

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Amoxicillin-clavulanate

**Description:** blood sampling in patients receiving amoxicillin-clavulanate as part of routine clinical care

**Name:** Amoxicillin-clavulanate

**Other Names:**

- Blood sampling

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- Piperacillin-tazobactam

**Description:** blood sampling in patients receiving piperacillin-tazobactam as part of routine clinical care.

**Name:** Piperacillin-tazobactam

**Other Names:**

- Blood sampling

**Type:** OTHER

#### Intervention 3

**Arm Group Labels:**

- Meropenem

**Description:** blood sampling in patients receiving meropenem as part of routine clinical care.

**Name:** Meropenem

**Other Names:**

- Blood sampling

**Type:** OTHER

#### Intervention 4

**Arm Group Labels:**

- Cefazolin

**Description:** blood sampling in patients receiving cefazolin as part of routine clinical care.

**Name:** Cefazolin

**Other Names:**

- Blood sampling

**Type:** OTHER

#### Intervention 5

**Arm Group Labels:**

- Vancomycin

**Description:** blood sampling in patients receiving vancomycin as part of routine clinical care.

**Name:** Vancomycin

**Other Names:**

- Blood sampling

**Type:** OTHER

#### Intervention 6

**Arm Group Labels:**

- Teicoplanin

**Description:** blood sampling in patients receiving teicoplanin as part of routine clinical care.

**Name:** Teicoplanin

**Other Names:**

- Blood sampling

**Type:** OTHER

#### Intervention 7

**Arm Group Labels:**

- Ciprofloxacin

**Description:** blood sampling and urine sampling in patients receiving ciprofloxacin as part of routine clinical care.

**Name:** Ciprofloxacin

**Other Names:**

- Blood sampling

**Type:** OTHER

#### Intervention 8

**Arm Group Labels:**

- Amikacin

**Description:** blood sampling in patients receiving amikacin as part of routine clinical care.

**Name:** Amikacin

**Other Names:**

- Blood sampling

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Amoxicillin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism

**Time Frame:** up to 1 month

**Description:** % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Cefazolin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism

**Time Frame:** up to 1 month

**Description:** % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Meropenem: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism

**Time Frame:** up to 1 month

**Description:** % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Piperacillin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism

**Time Frame:** up to 1 month

**Description:** % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens before or after extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Amoxicillin, piperacillin, meropenem, cefazolin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism

**Time Frame:** up to 1 month

**Description:** % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens before or after extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Cefazolin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism

**Time Frame:** up to 1 month

**Description:** % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens before or after extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Meropenem: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism

**Time Frame:** up to 1 month

**Description:** % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens before or after extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Piperacillin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism

**Time Frame:** up to 1 month

**Description:** % of patients for whom a fAUC/MIC target\>86 is achieved with the current dosing regimen off extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC)

**Time Frame:** up to 1 month

**Description:** % of patients in whom a AUC/MIC target 400-600 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC)

**Time Frame:** up to 1 month

**Description:** % of patients in whom a trough concentration between 20 to 30 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Teicoplanin: probability of target attainment with the target being a mimimal trough concentration

**Time Frame:** up to 1 month

**Description:** % of patients in whom an AUC/MIC of 900 is achieved with the current dosing regimen before or after extracorporeal membrane oxygenation in steady-state conditions

**Measure:** for teicoplanin: probability of target attainment with the target being an Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration Ratio (AUC/MIC)

**Time Frame:** up to 1 month

**Description:** % of patients in whom a target peak/MIC ratio of 8 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions

**Measure:** for amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC)

**Time Frame:** up to 1 month

**Description:** % of patients in whom the threshold for toxicity concentration\>5 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration

**Time Frame:** up to 1 month

**Description:** % of patients in whom the threshold for toxicity concentration\>5 mg/L is achieved with the current dosing regimen before or after extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration

**Time Frame:** up to 1 month

**Description:** % of patients in whom a target fAUC/MIC ratio of 399 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Amikacin: probability of target attainment with the target being a free Area-under-the-Concentration-Time Curve over Minimal Inhibitory Concentration ratio (AUC/MIC)

**Time Frame:** July 2026

**Description:** % of patients in whom a target fAUC/MIC ratio of 399 is achieved with the current dosing regimen before or after extracorporeal membrane oxygenation in steady-state conditions

**Measure:** Amikacin: probability of target attainment with the target being a free Area-under-the-Concentration-Time Curve over Minimal Inhibitory Concentration ratio (AUC/MIC)

**Time Frame:** July 2026

#### Secondary Outcomes

**Description:** The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a percentage of time during which the unbound concentration remains above the Minimal Inhibitory Concentration (MIC) of the micro-organism of at least 50% and a maximum concentration of 10 x MIC

**Measure:** Risk factors for underdosing during extracorporeal membrane oxygenation for beta-lactam antibiotics

**Time Frame:** up to 1 month

**Description:** The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of ciprofloxacin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a free Area-under the concentration-Time Curve of 86

**Measure:** Risk factors for underdosing during extracorporeal membrane oxygenation for ciprofloxacin

**Time Frame:** up to 1 month

**Description:** The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of vancomycin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a free Area-under the concentration-Time Curve of 200 to 300

**Measure:** Risk factors for under-and overdosing during extracorporeal membrane oxygenation for vancomycin

**Time Frame:** up to 1 month

**Description:** The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of teicoplanin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is an Area-under the concentration-Time Curve of 900

**Measure:** Risk factors for underdosing during extracorporeal membrane oxygenation for teicoplanin

**Time Frame:** up to 1 month

**Description:** The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of amikacin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a peak over Minimal Inhibitory Concentration Ratio of 8 to 10, trough concentration below 5 mg/L and Area under the Concentration Time Curve/MIC\>399

**Measure:** Risk factors for under-and overdosing during extracorporeal membrane oxygenation for amikacin

**Time Frame:** up to 1 month

**Description:** % of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in first dose conditions

**Measure:** Beta-lactam antibiotics (amoxicillin, piperacillin, meropenem, cefazolin): probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC)

**Time Frame:** up to 1 month

**Description:** % of patients for whom a fAUC/MIC target\>86 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions

**Measure:** Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC)

**Time Frame:** up to 1 month

**Description:** % of patients in whom a AUC/MIC target 400-600 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions

**Measure:** Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC)

**Time Frame:** up to 1 month

**Description:** % of patients in whom a trough concentration between 20 to 30 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions

**Measure:** Teicoplanin: probability of target attainment with the target being a mimimal trough concentration

**Time Frame:** up to 1 month

**Description:** % of patients in whom a target peak/MIC ratio of 8 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions

**Measure:** Amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC)

**Time Frame:** up to 1 month

**Description:** % of patients in whom the threshold for toxicity concentration\>5 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions

**Measure:** Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration

**Time Frame:** up to 1 month

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* patients admitted to the pediatric intensive care unit or cardiac intensive care unit
* patient age : 1,8 kg-15 years
* patient receiving antibiotic treatment (piperacillin-tazobactam, meropenem, amoxicillin-clavulanate, cephazolin, vancomycin, teicoplanin, ciprofloxacin, amikacin)
* intra-arterial or intravenous access other than the drug infusion line available for blood sampling (arterial line is preferred)
* extracorporeal membrane oxygenation circuit

Exclusion Criteria:

* no catheter in place for blood sampling
* absence of parental/patient consent
* known hypersensitivity to beta-lactam antibiotics and ciprofloxacin

**Maximum Age:** 15 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** pieter.decock@uzgent.be

**Name:** Pieter De Cock, PharmD

**Phone:** +32 9 332 29 69

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Brussel

**Contacts:**

***Contact 1:***

- **Email:** dominique.biarent@huderf.be

- **Name:** Biarent Dominique

- **Role:** CONTACT

***Contact 2:***

- **Email:** daphnevania.vens@huderf.be

- **Name:** Vens Daphne

- **Role:** CONTACT

**Country:** Belgium

**Facility:** Queen Fabiola Children's University Hospital

**Status:** RECRUITING

**Zip:** 1020

**Location 2:**

**City:** Ghent

**Contacts:**

***Contact 1:***

- **Email:** pieter.decock@uzgent.be

- **Name:** Pieter De Cock

- **Role:** CONTACT

**Country:** Belgium

**Facility:** University Hospital

**Status:** RECRUITING

**Zip:** 9000

**Location 3:**

**City:** Leuven

**Contacts:**

***Contact 1:***

- **Email:** yves.debaveye@uzleuven.be

- **Name:** Debaveye Yves

- **Role:** CONTACT

**Country:** Belgium

**Facility:** Universitair hospital

**Status:** RECRUITING

**Zip:** 3000

#### Overall Officials

**Official 1:**

**Affiliation:** University Hospital, Ghent

**Name:** Annick de Jaeger, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Intervention Browse Module - Ancestors

- ID: D000000900

- Term: Anti-Bacterial Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000059005

- Term: Topoisomerase II Inhibitors

- ID: D000059003

- Term: Topoisomerase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000065609

- Term: Cytochrome P-450 CYP1A2 Inhibitors

- ID: D000065607

- Term: Cytochrome P-450 Enzyme Inhibitors

- ID: D000065093

- Term: beta-Lactamase Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ANeo

- Name: Antineoplastic Agents

### Intervention Browse Module - Browse Leaves

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M3995

- Name: Amoxicillin

- Relevance: HIGH

- As Found: Colorectal

- ID: M17388

- Name: Vancomycin

- Relevance: HIGH

- As Found: Place

- ID: M6176

- Name: Ciprofloxacin

- Relevance: HIGH

- As Found: Endothelial

- ID: M1889

- Name: Meropenem

- Relevance: HIGH

- As Found: Expiratory

- ID: M5687

- Name: Cefazolin

- Relevance: HIGH

- As Found: Immune Response

- ID: M1938

- Name: Tazobactam

- Relevance: HIGH

- As Found: Ancillary studies

- ID: M13772

- Name: Piperacillin

- Relevance: HIGH

- As Found: Wide

- ID: M21710

- Name: Clavulanic Acid

- Relevance: HIGH

- As Found: Chemoembolization

- ID: M3924

- Name: Amikacin

- Relevance: HIGH

- As Found: Total Body Irradiation

- ID: M1885

- Name: Piperacillin, Tazobactam Drug Combination

- Relevance: HIGH

- As Found: Paroxysmal Atrial Fibrillation

- ID: M21845

- Name: Amoxicillin-Potassium Clavulanate Combination

- Relevance: HIGH

- As Found: Treatment failure

- ID: M19621

- Name: Teicoplanin

- Relevance: HIGH

- As Found: Soda

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

- ID: M6204

- Name: Clavulanic Acids

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M30537

- Name: Cytochrome P-450 Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M30450

- Name: beta-Lactamase Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000000658

- Term: Amoxicillin

- ID: D000014640

- Term: Vancomycin

- ID: D000002939

- Term: Ciprofloxacin

- ID: D000077731

- Term: Meropenem

- ID: D000002437

- Term: Cefazolin

- ID: D000078142

- Term: Tazobactam

- ID: D000010878

- Term: Piperacillin

- ID: D000019818

- Term: Clavulanic Acid

- ID: D000000583

- Term: Amikacin

- ID: D000077725

- Term: Piperacillin, Tazobactam Drug Combination

- ID: D000019980

- Term: Amoxicillin-Potassium Clavulanate Combination

- ID: D000017334

- Term: Teicoplanin

### Misc Info Module

- Version Holder: 2024-05-31
