Amoxicillin alone versus amoxicillin/clavulanate for community-acquired pneumonia in patients aged 65 years or older, and hospitalized in a non-intensive care unit ward: a non-inferiority randomized controlled trial _ CAPTAIN

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

25 Apr 2024 → ongoing

Decision date (initial)

2024-01-08

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS PHRC National

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

to investigate non-inferiority in terms of clinical efficacy among patients aged 65 years or older, hospitalized in a non-ICU ward for a CAP, and treated with narrow-spectrum (amoxicillin) versus broad-spectrum (amoxicillin/clavulanate) antimicrobial therapy, at Day 30 since hospital admission

Secondary objectives 12

1. Rates of early clinical response at Day 3
2. Clinical cure after the end of treatment
3. To investigate total duration of antibiotic treatment, i.e., the total number of days with antibiotics during the Day 30 follow-up after hospital admission
4. To investigate all-cause mortality at Day 30 after hospital admission
5. To investigate the rate of polymerase chain reaction (PCR)-positive Clostridium difficile among patients with diarrhea
6. To investigate in-hospital mortality
7. To investigate ICU transfer during the Day 30 follow-up
8. To investigate CAP recurrence and hospital readmissions up to day 30 from hospital admission
9. To investigate adverse events attributable to antibiotics up to day 30 from hospital admission
10. To investigate compliance with the antibiotic treatment
11. To investigate length of hospital stay
12. To investigate the agreement between the early clinical response endpoint and the investigator’s clinical judgment

Conditions and MedDRA coding

Patients aged 65 years or older, hospitalized in a non-ICU ward for a community acuquired pneumonia, and treated with narrow-spectrum versus broad-spectrum antimicrobial therapy

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patient aged 65 years or older with or without comorbidities defined by chronic diseases in immunocompetent patients
2. Patient admitted to the hospital for a CAP defined by at least two clinical signs of pneumonia (cough, sputum production, dyspnea, tachypnea, or pleuritic pain, abnormal lung auscultatory sounds, fever (temperature > 38°C) or hypothermia (< 36°C)) and radiological evidence of a new infiltrate confirming pneumonia
3. Written informed consent obtained from patient prior to participation in the study (if the patient is unable to express in writing: consent by a trusted person)
4. Patient understanding oral and written French
5. Patients 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 a medical staff belonging to the investigational site

Exclusion criteria 20

1. Patient requiring ICU admission
2. Diagnosis confirmed of SAR-Cov2 infection (PCR Test, covid antigen rapid test, or chest computed tomography (CT) scan)
3. Participation to another interventional study and having an exclusion period that is still in force during the screening phase or expected participation to another interventional study during participation to the CAPTAIN study
4. Estimated Glomerular Filtration Rate < 30 ml/min
5. Known immunosuppression (asplenia, neutropenia, agammaglobulinemia, transplant, myeloma, lymphoma, known HIV and CD4<200/mm3)
6. Exacerbation of chronic obstructive pulmonary disease
7. Life-threatening presentation expected to lead to possible imminent death
8. Suspected atypical bacteria requiring combined antibiotics therapy
9. Legionella suspected
10. Subjects with clinical or epidemiological environment leading to suspect a healthcare associated pneumonia with antibiotic resistant pathogen (including long-term care facility)
11. Patient known to be colonized with Pseudomonas aeruginosa or Enterobacteriaceae in the respiratory tract
12. Suspicion of aspiration pneumonia
13. Signs of severe CAP (abscess, massive pleural effusion, serious chronic respiratory insufficiency, ICU admission)
14. History of bacterial pneumonia less than 1 month prior to study inclusion
15. History of jaundice/hepatic impairment associated with amoxicillin/clavulanate acid
16. History of hypersensitivity or allergy to beta-lactam or to any excipients included in study antibiotics
17. Subject without health insurance
18. Subject without home address or difficulty in terms of follow-up (vacation, job transfer, geographical distance, lack of motivation)
19. Patient under judicial protection
20. Administration of any antibiotic treatment for more than 24 hours before inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. clinical success rate at Day 30 (Montassier et al., 2019) since admission, defined as survival after completion of antibiotic treatment course, resolution of signs and symptoms of the infection (cough, purulent sputum production, dyspnea, or pleuritic chest pain) present at baseline with no new symptoms or complications attributable to CAP and no need for further antibacterial therapy

Secondary endpoints 12

1. Early clinical response will be defined as survival with improvement of one or more levels relative to baseline in two or more symptoms of CAP and no worsening of one or more levels in other symptoms of community-acquired bacterial pneumonia, without receipt of rescue antibacterial therapy
2. The proposed endpoint of clinical cure after the end of treatment is defined as resolution in relevant signs and symptoms reported at baseline, no worsening of symptoms, and no change in antimicrobial regimen
3. Days taking antibiotics from the first dose until the interruption of any antibiotic treatment during hospitalization and at late follow-up at Day 30 after hospital admission (to identify the use of any other antibiotic after hospital discharge defined as no IV, regain of autonomy identical to baseline, good clinical response and favorable evolution following initiation of antibiotics, other criteria left at the discretion of the investigators according to centers’ practices)
4. All-cause mortality at Day 30 after hospital admission
5. Number of positive polymerase chain reaction (PCR)-positive Clostridium difficile among patients with diarrhea
6. Number of deaths during hospitalization
7. Number of patients transferred to the ICU during the Day 30 follow- up
8. Number of hospital readmissions and CAP recurrence up to day 30 from hospital admission
9. Number of adverse events attributable to antibiotics and number of days with adverse events up to day 30 from hospital admission
10. Number of days of antibiotic treatment taken
11. Total number of days in the hospital during the Day 30 follow-up
12. Agreement between early clinical response (main endpoint) and the investigator’s clinical judgement (clinical success or clinical failure)

Investigational products

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

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Professor Emmanuel MONTASSIER

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Professor Emmanuel MONTASSIER

Locations

1 EU/EEA country · 19 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 10 files

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

Application history

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