Customized Antibiotic Treatment Duration Among Hospitalized Patients with Moderately Severe Community-Acquired Pneumonia [Cat-Cap]

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] - Bacterial Infections and Mycoses [C01]

Trial duration

12 Feb 2024 → ongoing

Decision date (initial)

2023-12-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS - French Ministry of Health

External identifiers

EU CT number

2023-504208-27-00

ClinicalTrials.gov

NCT05903352

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate if the efficacy of an experimental strategy on antibiotic treatment duration based on stopping treatment when stability criteria are reached after at least 48 h of treatment, is non-inferior to the efficacy of standard antibiotic duration in CAP patients treated in the hospital setting.

Secondary objectives 3

1. To study if the efficacy of our experimental strategy on antibiotic treatment duration compared to standard of care in CAP patients treated in the hospital setting is non-inferior in terms of: • Persistence of cure at Day 30 of antibiotic treatment • All-cause mortality rate on Day 30 of antibiotic treatment • Patients evolution of pneumonia symptoms and quality of life via 2 scores (CAP score, CAP Sym) at Day 0 of treatment (retrospectively), at stability (Day S), at Day 7 , at Day 15, and at Day 30 of antibiotic treatment.
2. To compare between the 2 study arms at Day 30 of antibiotic treatment: • The total duration of antibiotic treatment (targeting CAP and for all indications); • The length of initial hospital stay (at end of follow-up); • The frequency and severity of adverse events during the 30 days after the start of treatment
3. To explore the impact of reduced antibiotic treatment duration for CAP on the oropharyngeal resistome.

Conditions and MedDRA coding

Community-acquired pneumonia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Adult patient (≥18 years old)
2. Admitted to hospital for suspected CAP defined by the presence of at least 2 of the following diagnostic clinical criteria: o Fever (temperature > 38°C) or hypothermia (< 36°C) o Dyspnea o Cough o Production of purulent sputum o Crackles
3. Radiological evidence of a new infiltrate (chest X-ray or CT scan)
4. Treated for a minimum of 48 hours and a maximum of 7 days with antibiotics chosen according to the French recommendations for suspected CAP (excluding azithromycin due to its prolonged half-life) and currently under antibiotic treatment for his suspected CAP (i.e. the last dose of ATB has been administered to the patient less than 24 hours ago)Patient presenting a clinical response within the last 24 hours defined by the presence of all the following criteria: o apyrexia (T°C ≤ 37.8) o heart rate < 100/min o respiratory rate < 24/min, according to the patient's usual mode of oxygenation, o arterial oxygen saturation ≥ 92%, according to the patient's usual mode of oxygenation, o systolic blood pressure ≥ 90mmHg, The last occurring of these criteria must have appeared within the last 24 hours.
5. No other site of infection besides respiratory
6. Affiliated to Health insurance or patients with government medical aid called AME
7. Has given informed consent
8. Patient understanding oral and written French, or presence of a relative who can explain and help him complete the study documents (Patient should be able to call and to answer to a phone call or to be with a relative who can help him to call or to answer questions notably raised by medical staff belonging to the investigational site)
9. Patient presenting a clinical response within the last 24 hours (up to 7 days after the start of antibiotic treatment, if planned treatment duration > 7 days) defined by the presence of all the following criteria: apyrexia (T°C ≤ 37.8), heart rate ≤ 100/min, respiratory rate < 24/min, arterial oxygen saturation ≥ 90% on room air, systolic blood pressure ≥ 90mmHg
10. Negative viral respiratory testing (positive viral testing will be allowed only if bacterial documentation is confirmed by PCR or culture)
11. Antibiotic treatment anticipated to be prescribed for a minimum of one additional day if the patient is not randomized into the experimental group

Exclusion criteria 18

1. Signs of severe CAP (abscess, massive pleural effusion, serious chronic respiratory insufficiency insufficiency with long-term oxygen therapy, ICU admission)
2. Treatment of suspected CAP with azithromycin (due to its prolonged half-life)
3. Concomitant steroid treatment (only for patients treated with fluoroquinolones antibiotics)
4. Pregnant or breastfeeding woman
5. More than 24 hours of efficacious antibiotics prior to hospital admission (except for oral fosfomycin, furadantin and pivmecillinam used in accordance with the marketing authorisations)
6. Positive family history of aneurysm disease or congenital heart valve disease, patients diagnosed with pre-existing aortic aneurysm and/or dissection or heart valve disease, patients with presence of other risk factors or conditions predisposing: for both aortic aneurysm and dissection and heart valve regurgitation/incompetence (e.g. connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behcet´s disease, hypertension, rheumatoid arthritis) or additionally .for aortic aneurysm and dissection (e.g. vascular disorders such as Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren’s syndrome) or additionally .for heart valve regurgitation/incompetence (only for patients treated with fluoroquinolones antibiotics)
7. Life expectancy < 1 month
8. Patient under legal guardianship (French “tutelle” or “curatelle”)
9. Patient without fixed address
10. Patient enrolled in another interventional clinical trial on antibiotic treatments
11. Known immunosuppression (asplenia, neutropenia, agammaglobulinemia, bone marrow transplant, myeloma, lymphoma, known HIV and CD4<200/mm3)
12. Suspected or confirmed legionellosis
13. Any other infection necessitating concomitant antibiotic treatment (except if treated by oral fosfomycin, furadantin and pivmecillinam used in accordance with the marketing authorisations)
14. Confirmed aspiration pneumonia or healthcare-associated pneumonia
15. Contra-indications to study antibiotics
16. Patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products (for patients treated with fluoroquinolones)
17. History of bacterial pneumonia less than 1 month prior to study inclusion
18. Bronchopulmonary diseases : cystic fibrosis; severe bronchiectasis; lung cancer under active anti-cancer treatment (patients considered in remission and having received no treatment (chemotherapy, radiotherapy, targeted therapy or immunotherapy) for at least 6 months may be included); ongoing tuberculosis or major sequelae of tuberculosis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of cure at Day 15 after treatment initiation Cure at Day 15 will be defined by the association of: 1.Persistence of stability criteria (body temperature ≤ 37.8°C; heart rate ≤ 100/min; systolic blood pressure > 90mmHg; oxygen saturation ≥ 92%; respiratory rate < 24/min; normal mental status); 2.No additional antibiotic treatment, targeting CAP, taken after the end of initial antibiotic treatment. Patients dead or not cured as defined above, will be classified as failure at Day 15.

Secondary endpoints 8

1. Rate of cure at Day 30 after the start of treatment defined by the association of: persistence of stability criteria (body temperature ≤ 37.8°C; heart rate ≤ 100/min; systolic blood pressure > 90mmHg; O2 saturation ≥ 90% on room air; respiratory rate < 24/min; normal mental status); absence of additional antibiotic treatment needed after the end of initial antibiotic treatment ((except for oral fosfomycin, furadantin and pivmecillinam).
2. All-cause mortality on Day 30 after the start of antibiotic treatmen
3. Patients' evolution of pneumonia symptoms and quality of life (CAP Score / CAP Sym) at Day 0 of treatment (retrospectively), at stability (Day S), at Day 7, at Day 15, and at Day 30 of antibiotic treatment;
4. Duration of antibiotic treatment targeting CAP during the 30 days after the start of treatment;
5. Duration of antibiotic treatment for all indications during the 30 days after the start of treatment
6. Length of initial hospital stay
7. Frequency and severity of adverse events during the 30 days after the start of treatment.
8. Analysis of microbiome and resistance genes at Day S and Day 30

Investigational products

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

Test 7

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

Pr Aurélien DINH

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Aurélien DINH

Locations

1 EU/EEA country · 18 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 23 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