Overview
Sponsor-declared trial summary
Phase
Phase III and Phase IV (Integrated)
Status
Ongoing, recruiting
Participants planned
988
Countries
1
Sites
18
Sepsis
To determine if using a new dosing strategy improves clinical outcome of sepsis patients in the ICU.
Key facts
- Sponsor
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Bacterial Infections and Mycoses [C01]
- Trial duration
- 3 Jan 2025 → ongoing
- Decision date (initial)
- 2024-09-30
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Erasmus MC
External identifiers
- EU CT number
- 2024-512950-13-00
- WHO UTN
- U1111-1308-9223
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To determine if using a new dosing strategy improves clinical outcome of sepsis patients in the ICU.
Conditions and MedDRA coding
Sepsis
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- - ≥18 years of age
- - Receiving intravenous antibiotic therapy of the target drugs (including continuous infusion of beta-lactam antibiotics)
- - Primary infection
- - Admitted to the ICU
- - Meeting the Sepsis-3 criteria for septic shock: sepsis in addition to shock requiring the start of vasopressors to maintain a mean arterial pressure 65 mm Hg or greater, and a serum lactate level greater than 2.0 mmol/L following “adequate fluid resuscitation”.
Exclusion criteria 8
- - Patient or legal representative not available to give informed consent within three days after admittance
- - Pregnancy
- - Admittance for burn wounds
- - Patients receiving target antibiotics only as prophylaxis within the context of Selective Di-gestive tract Decontamination (SDD)
- - Enrolment in another interventional trial
- - Patient received the study antibiotic for more than 24 hours before inclusion
- - Patient receiving extracorporeal membrane oxygenation (ECMO)
- - Patient is already treated with double dose of antibiotics based on suspected infection
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 28-day mortality
Secondary endpoints 10
- • Blood levels of antibiotics at 24, 48 and 72 hours after start therapy.
- • Infection parameters (CRP, procalcitonin, white blood cell count).
- • 365-day mortality
- • 90-day mortality
- • Hospital length of stay
- • ICU length of stay
- Post study calculation of the costs in both study groups.
- EQ5D questionnaire 3 and 12 months after admission
- Number of AEs, SAEs and SUSARs
- Delta SOFA (T0- T3)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 10
Ceftazidim Fresenius Kabi 500 mg poeder voor oplossing voor injectie
PRD1962867 · Product
- Active substance
- Ceftazidime Pentahydrate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 12 g gram(s)
- Max total dose
- 36 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DD02 — -
- Marketing authorisation
- RVG 101815
- MA holder
- FRESENIUS KABI NEDERLAND B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD910696 · Product
- Active substance
- Amoxicillin
- Substance synonyms
- AMOXICILLINE, AMOXICILLINUM
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 8 g gram(s)
- Max total dose
- 24 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CR02 — AMOXICILLIN AND ENZYME INHIBITOR
- Marketing authorisation
- RVG 28026
- MA holder
- SANDOZ B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Ceftriaxon Fresenius Kabi 1 g poeder voor oplossing voor injectie of infusie
PRD408953 · Product
- Active substance
- Ceftriaxone Sodium
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 4 g gram(s)
- Max total dose
- 12 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DD04 — -
- Marketing authorisation
- RVG 100048
- MA holder
- FRESENIUS KABI NEDERLAND B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Floxapen, poeder voor oplossing voor injectie 250 mg, 500 mg en 1 g
PRD10189022 · Product
- Active substance
- Flucloxacillin
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 12 g gram(s)
- Max total dose
- 36 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CF05 — FLUCLOXACILLIN
- Marketing authorisation
- RVG 05990
- MA holder
- AUROBINDO PHARMA B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD2193724 · Product
- Active substance
- Amoxicillin
- Substance synonyms
- AMOXICILLINE, AMOXICILLINUM
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 12 g gram(s)
- Max total dose
- 36 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CA04 — AMOXICILLIN
- Marketing authorisation
- RVG 57326
- MA holder
- CENTRAFARM B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Meropenem Fresenius Kabi 1 g poeder voor oplossing voor injectie of infusie
PRD3771893 · Product
- Active substance
- Meropenem Trihydrate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 6 g gram(s)
- Max total dose
- 18 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DH02 — MEROPENEM
- Marketing authorisation
- BE374114
- MA holder
- FRESENIUS KABI NV/SA
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cefotaxim 1000 mg PCH, poeder voor oplossing voor injectie
PRD4131800 · Product
- Active substance
- Cefotaxime
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 12 g gram(s)
- Max total dose
- 36 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DD01 — -
- Marketing authorisation
- RVG 27751
- MA holder
- PHARMACHEMIE BV
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cefuroxim Hikma 1500 mg poeder voor oplossing voor injectie of infusie
PRD10470970 · Product
- Active substance
- Cefuroxime
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 9 g gram(s)
- Max total dose
- 27 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DC02 — -
- Marketing authorisation
- RVG 20590
- MA holder
- HIKMA FARMACÊUTICA (PORTUGAL), S.A.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Piperacilline/Tazobactam Fresenius Kabi 2 g/0,25 g poeder voor oplossing voor infusie
PRD767313 · Product
- Active substance
- Piperacillin Sodium
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 24 g gram(s)
- Max total dose
- 72 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CR05 — PIPERACILLIN AND ENZYME INHIBITOR
- Marketing authorisation
- BE324073
- MA holder
- FRESENIUS KABI NV/SA
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Meropenem CF 1000 mg, poeder voor oplossing voor injectie of infusie
PRD1864046 · Product
- Active substance
- Meropenem
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 6 g gram(s)
- Max total dose
- 18 g gram(s)
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DH02 — MEROPENEM
- Marketing authorisation
- RVG 109675
- MA holder
- CENTRAFARM B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Sponsor organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Address
- Dr. Molewaterplein 40
- City
- Rotterdam
- Postcode
- 3015 GD
- Country
- Netherlands
Scientific contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Mirte Horstink
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Mirte Horstink
Locations
1 EU/EEA country · 18 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 988 | 18 |
| Rest of world | — | 0 | — |
Investigational sites
Jeroen Bosch Ziekenhuis Stichting
Intensive Care, Henri Dunantstraat 1, 5223 GZ, 'S-Hertogenbosch
Noordwest Ziekenhuisgroep Stichting
Intensive Care, Wilhelminalaan 12, 1815 JD, Alkmaar
Medisch Spectrum Twente
Intensive Care, Koningsplein 1, 7512 KZ, Enschede
Stichting Elisabeth-Tweesteden Ziekenhuis
Intensive Care, Hilvarenbeekseweg 60, 5022 GC, Tilburg
Spaarne Gasthuis Stichting
Intensive Care, Spaarnepoort 1, 2134 TM, Hoofddorp
Stichting OLVG
Intensive Care, Oosterpark 9, 1091 AC, Amsterdam
Tergooiziekenhuizen
Intensive Care, Van Riebeeckweg 212, 1213 XZ, Hilversum
Amphia Hospital
Intensive Care, Molengracht 21, 4818 CK, Breda
IJsselland Ziekenhuis
Intensive Care, Prins Constantijnweg 2, 2906 ZC, Capelle Aan Den Ijssel
Medisch Centrum Leeuwarden B.V.
Intensive Care, Henri Dunantweg 2, 8934 AD, Leeuwarden
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Pharmacy, Dr. Molewaterplein 60, 3015 GJ, Rotterdam
Albert Schweitzer Ziekenhuis
Intensive Care, Albert Schweitzerplaats 25, 3318 AT, Dordrecht
Maasstad Ziekenhuis Stichting
Intensive Care, Maasstadweg 21, 3079 DZ, Rotterdam
Reinier de Graaf Groep
Intensive Care, Reinier De Graafweg 5, 2625 AD, Delft
Ikazia Ziekenhuis
Intensive Care, Montessoriweg 1, 3083 AN, Rotterdam
Het Van Weel-Bethesda Ziekenhuis
Intensive Care, Stationsweg 22, 3247 BW, Dirksland
Isala Klinieken Stichting
Intensive Care, Dokter Van Heesweg 2, 8025 AB, Zwolle
Haaglanden Medisch Centrum Stichting
Intensive Care, Lijnbaan 32, 2512 VA, 'S-Gravenhage
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2025-01-03 | 2025-01-03 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 17 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-512950-13-00 | 2.4 |
| Recruitment arrangements (for publication) | K1_Recuitment arrangements | 1.2 |
| Recruitment arrangements (for publication) | K2_Infographic PIF | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adult patient | 2.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adult representative | 2.2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Amoxicilline | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Amoxicilline_clavulaanzuur | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Cefotaxim | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Ceftazidim | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Ceftriaxon | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Cefuroxim | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Flucloxacilline | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Meropenem CF | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Meropenem Fresenius | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Piperacilline_Tazobactam | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ENG 2024-512950-13-00 | 2.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis NL 2024-512950-13-00 | 2.0 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-11 | Netherlands | Acceptable 2024-09-30
|
2024-09-30 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-12-09 | Netherlands | Acceptable 2025-01-16
|
2025-01-16 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-03-05 | Netherlands | Acceptable | 2025-03-27 |
| 4 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-04-24 | Netherlands | Acceptable 2025-06-26
|
2025-06-26 |
| 5 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-07-10 | Netherlands | Acceptable | 2025-07-22 |
| 6 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-12-04 | Netherlands | Acceptable 2026-01-05
|
2026-01-05 |