Combination lock01 - Impact of aminoglycosides-based antibiotics combination and protective isolation on outcomes in critically-ill neutropenic patients with sepsis:A randomized 2 by 2 factorial design randomized pragmatic trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

21 Sep 2022 → ongoing

Decision date (initial)

2024-08-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

DGOS

External identifiers

EU CT number

2024-514042-36-00

EudraCT number

2019-003016-32

ClinicalTrials.gov

NCT05443854

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the impact on day-90 mortality of two strategies, separately, using a 2x2 factorial design RCT:
• Intervention 1 - routine association of aminoglycoside to initial antibiotic therapy when compared to standard of care
• Intervention 2 - lack of routine use of protective isolation when compared to standard of care

Secondary objectives 10

1. Day-28 and hospital outcome
2. on Incidence, severity and duration of AKI
3. Incidence of clinically apparent loss of hearing
4. Rate of adherence of hand hygiene
5. Rate of selected adverse events
6. Rate of nosocomial bacterial, viral and fungal infection episodes
7. Organ support during ICU stay and organ support duration
8. Failure of initial antibiotic therapy
9. Antibiotic duration
10. Rate of aminoglycosides overdosage and overuse

Conditions and MedDRA coding

Adult patients admitted to intensive care

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years
2. Admitted in one of the participating ICU
3. Sepsis or septic shock as defined by SEPSIS3 definition
4. Underlying tumor, allogeneic stem cell transplantation or hematological malignancy
5. Neutropenia (defined by either absolute neutrophil count <500/mm3 or leucocytes <1000/mm3) related to an underlying malignancy or its treatment
6. Informed or deferred consent

Exclusion criteria 11

1. Pregnancy and breastfeeding
2. Moribund patients (death expected within 48 hours by attending physician)
3. Previous participation to this study
4. No affiliation to social security
5. Patients under legal protection according to French Law
6. Patient having received more than 1 injection of aminoglycosides in the 3 days preceding ICU admission
7. Contraindication to aminoglycosides as mentioned in SpC section 4.3
8. Hypersensitivity to amikacin, to other antibiotics from the aminoglycoside family, or to any excipient from the amikacin used
9. Patients with documented allergy to aminoglycosides
10. Myasthenia gravis
11. Concomitant administration of intravenous Polymyxin - Delay between onset of sepsis and inclusion>24 hours

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Day-90 mortality

Secondary endpoints 12

1. Day-28 and hospital mortality
2. Incidence and severity of AKI according to KDIGO definition
3. Major Adverse Kidney Events at day-28 and day 90 (composite of death, new renal replacement therapy, or persistent renal dysfunction)
4. Incidence of clinically apparent loss of hearing at end of ICU stay and day 90
5. Rate of adherence to adequate hand hygiene as assessed by external observer
6. Incidence density of selected serious adverse events including unexpected cardiac arrest
7. Incidence density of new bacterial, viral or fungal episode
8. Number of days free from organ support therapy (mechanical ventilation, vasopressors or RRT) at day 28
9. Rate of clinical cure
10. Frequency of initial antibiotic therapy inadequate as regard to microbiological documentation.
11. Number of day free of antibiotic therapy at day-28
12. Duration of aminoglycoside therapy, rate of aminoglycoside overdosage according to residual concentration and overuse when compared to experts recommendations

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigateur Coordonnateur

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigateur Coordonnateur

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 9 files

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

Application history

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