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Customized Antibiotic Treatment Duration Among Hospitalized Patients With Moderately Severe Community-Acquired Pneumonia (CAT-CAP)

Primary Purpose

Community-Acquired Pneumonia

Status

Not yet recruiting

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Stop antibiotic

Continue the antimicrobial treatment

About this trial

This is an interventional treatment trial for Community-Acquired Pneumonia focused on measuring Community-Acquired Pneumonia, Antibiotic treatment duration, Antibiotic resistance, Infectious diseases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Adult patient (≥18 years old) Admitted to hospital for suspected CAP defined by the presence of at least 2 of the following diagnostic clinical criteria: Fever (temperature > 38°C) or hypothermia (< 36°C) Dyspnea Cough Production of purulent sputum Crackles Radiological evidence of a new infiltrate (chest X-ray or CT scan) Negative viral respiratory testing Treated for a minimum of 48 hours with antibiotics (excluding azithromycin due to its prolonged half-life)Presenting with an early 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/minrespiratory rate < 24/min, according to the patient's usual mode of oxygenation,arterial oxygen saturation ≥ 92%, according to the patient's usual mode of oxygenation,Patient 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: apyrexia (T°C ≤ 37.8) heart rate < 100/min respiratory rate < 24/min, according to the patient's usual mode of oxygenation, arterial oxygen saturation ≥ 92%, according to the patient's usual mode of oxygenation, systolic blood pressure ≥ 90mmHg, The last occurring of these criteria must have appeared within the last 24 hours. The antibiotic treatment for suspected CAP has started at least 48 hours ago and at most 6 days ago No other site of infection besides respiratory Affiliated to Health insurance Has given informed consent Patient understanding oral and written French, or presence of a relative who can explain and help him complete the study documents Exclusion Criteria: Signs of severe CAP (abscess, massive pleural effusion, serious chronic respiratory insufficiency) Known immunosuppression (asplenia, neutropenia, agammaglobulinemia, transplant, myeloma, lymphoma, known HIV and CD4<200/mm3) Suspected or confirmed legionellosis Any other infection necessitating concomitant antibiotic treatment Confirmed or suspected aspiration pneumonia or healthcare-associated pneumonia Treatment of suspected CAP with azithromycin (due to its prolonged half-life) Concomitant steroid treatment (only for patients treated with fluoroquinolones antibiotics) Pre-existing aortic aneurysm or dissection, family history of aortic aneurysm or dissection, Marfan syndrome, Ehlers-Danlos syndrome, Takayasu arthritis, uncontrolled arterial hypertension, atherosclerosis (only for patients treated with fluoroquinolones antibiotics) Pregnant or breastfeeding woman Life expectancy < 1 month Patient under legal guardianship (French "tutelle" or "curatelle") Patient without fixed address Patient enrolled in another interventional clinical trial on CAP treatment

Sites / Locations

Infectious diseases department, Raymond-Poincaré Hospital - APHP

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Antibiotic treatment

Interruption of treatment

Arm Description

Antibiotic treatment duration left to the physician's judgment (usual practice: total treatment duration between 5 to 10 days according to French guidelines; more than 7 days of treatment should be justified).

Interruption of treatment based on the patient reaching all of the following 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 (27)), with a treatment duration no shorter than 48 h.

Outcomes

Primary Outcome Measures

Rate of cure at Day 15 after treatment initiation

Cure at Day 15 will be defined by the association of: 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); No additional antibiotic treatment, targeting CAP, taken after the end of initial antibiotic treatment. Patients who died, or are not cured as defined above, will be classified as failure at Day 15.

Secondary Outcome Measures

Rate of cure at Day 30

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 ≥ 92%; respiratory rate < 24/min; normal mental status); absence of additional antibiotic treatment needed after the end of initial antibiotic treatment.

Mortality on Day 30

All-cause mortality on Day 30 after the start of antibiotic treatment.

Patients' evolution of pneumonia symptoms

Patients' evolution of pneumonia symptoms by CAP Score at Day 0 of treatment (retrospectively), at stability (Day S), at Day 7, at Day 15, and at Day 30 of antibiotic treatment.

Patients' evolution of pneumonia symptoms

Patients' evolution of pneumonia symptoms and quality of life by CAP Sym: validated self-questionnaires filled at Day 0 of treatment (retrospectively), at stability (Day S), at Day 7, at Day 15, and at Day 30 of antibiotic treatment.

Duration of antibiotic treatment targeting CAP

Duration of antibiotic treatment targeting CAP during the 30 days after the start of treatment.

Duration of antibiotic treatment for all indications

Duration of antibiotic treatment for all indications during the 30 days after the start of treatment.

Length of hospitalization

Length of initial hospital stay

Incidence of adverse event

Frequency and severity of adverse events during the 30 days after the start of treatment

Number of resistance genes

Calculating for each patient, the number of resistance genes normalised against the quantity of total bacterial DNA, the bacterial richness and diversity, among 300 patients.

Full Information

NCT ID

NCT05903352

First Posted

June 6, 2023

Last Updated

July 24, 2023

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT05903352

Brief Title

Customized Antibiotic Treatment Duration Among Hospitalized Patients With Moderately Severe Community-Acquired Pneumonia

Acronym

CAT-CAP

Official Title

Customized Antibiotic Treatment Duration Among Hospitalized Patients With Moderately Severe Community-Acquired Pneumonia

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

August 2023 (Anticipated)

Primary Completion Date

December 2026 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary objective of the study is 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. As the secondary objectives, the study aims 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. To compare between the 2 study arms at Day 30 of antibiotic treatment: The duration of antibiotic treatment; The length of hospital stay; The frequency and severity of adverse events during the 30 days after the start of treatment. To explore the impact of reduced antibiotic treatment duration for CAP on the oropharyngeal resistome.

Detailed Description

Recent studies have suggested that community-acquired pneumonia (CAP) can be successfully treated with short-course antibiotic regimen when clinical improvement is rapidly obtained. Even if clinical response is obtained in 3 days in the majority of cases, it can vary widely among patients suggesting "one duration does not fit all". An individualised duration of therapy depending on the patient's response could help to ensure bacterial eradication while avoiding unnecessary antibiotic exposure and thus reduce antibiotic resistance. At present, this strategy has never been tested. This is a phase III, pragmatic, non-inferiority randomised (1:1) national multicentre trial. Population of study participants will be patients admitted to hospital with suspected CAP and in need for antibiotics. There is no need to establish a DSMB for this trial. The antibiotic treatments prescribed during this study are treatments used in current practice, with well-known adverse drug reactions. Furthermore, a 3-day treatment duration has already been studied in 2 previous randomized clinical trials, showing its safety for hospitalized CAP. Statistical analysis: Statistical inference for non-inferiority will be based on the confidence intervals (CI) of the difference in Day 15 cure proportions [proportion in reference arm - proportion in experimental arm] accounting for randomisation stratification factors (centre and delay from Day 0 to Day S (≤ 3 days or > 3 days). The inferiority hypothesis will be rejected and non-inferiority will be claimed if the upper bound of the 95%CI of the difference is ≤ 10%. Secondary efficacy endpoints evaluating the evolution of symptoms will be analysed using either a GMM or a GEE for categorical and continuous variables, respectively. Other quantitative variables will be compared using the Student t-test (or a non-parametric test if the distribution remains skewed following transformation), while categorical variables will be analysed using either the Chi-squared or the Fisher-exact tests. All statistical tests will be performed with a level of significance of 5%, except the primary endpoint which be analysed with a 2.5% level of significance.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Community-Acquired Pneumonia

Keywords

Community-Acquired Pneumonia, Antibiotic treatment duration, Antibiotic resistance, Infectious diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

All eligible patients with confirmed CAP and willing to participate will be included and randomly assigned (1:1 ratio) by the investigator, to either continue the antimicrobial treatment for a duration predetermined by the investigator (usual practice, at least 3 days of treatment in total), or to stop the antibiotic treatment.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

328 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Antibiotic treatment

Arm Type

Placebo Comparator

Arm Description

Arm Title

Interruption of treatment

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

Stop antibiotic

Intervention Description

Stop the antibiotic treatment on day S (stability criteria reached for 24 h or within 48 hours after the start of antibiotic treatment).

Intervention Type

Drug

Intervention Name(s)

Continue the antimicrobial treatment

Intervention Description

Continue the antimicrobial treatment for a duration predetermined by the investigator (usual practice, at least 5 days of treatment in total).

Primary Outcome Measure Information:

Title

Rate of cure at Day 15 after treatment initiation

Description

Time Frame

Day 15

Secondary Outcome Measure Information:

Title

Rate of cure at Day 30

Description

Time Frame

Day 30

Title

Mortality on Day 30

Description

All-cause mortality on Day 30 after the start of antibiotic treatment.

Time Frame

Day 30

Title

Patients' evolution of pneumonia symptoms

Description

Patients' evolution of pneumonia symptoms by CAP Score at Day 0 of treatment (retrospectively), at stability (Day S), at Day 7, at Day 15, and at Day 30 of antibiotic treatment.

Time Frame

Day-0, Day S, Day 7, at Day 15, and at Day 30

Title

Patients' evolution of pneumonia symptoms

Description

Time Frame

Day 15 and Day 30

Title

Duration of antibiotic treatment targeting CAP

Description

Duration of antibiotic treatment targeting CAP during the 30 days after the start of treatment.

Time Frame

Day 30

Title

Duration of antibiotic treatment for all indications

Description

Duration of antibiotic treatment for all indications during the 30 days after the start of treatment.

Time Frame

Day 30

Title

Length of hospitalization

Description

Length of initial hospital stay

Time Frame

Day 30

Title

Incidence of adverse event

Description

Frequency and severity of adverse events during the 30 days after the start of treatment

Time Frame

Day 30

Title

Number of resistance genes

Description

Calculating for each patient, the number of resistance genes normalised against the quantity of total bacterial DNA, the bacterial richness and diversity, among 300 patients.

Time Frame

Day S and Day 30

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Aurélien Dinh, MD, PhD

Phone

+ 33 (0)1 47 10 44 32

aurelien.dinh@aphp.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Jacques Ropers, PharmD

Phone

+ 33 01 42 16 03 48

jacques.ropers@aphp.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Aurélien Dihn, MD, PhD

Organizational Affiliation

Infectious diseases department, Raymond-Poincaré Hospital - APHP

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jacques Ropers, PharmD

Organizational Affiliation

Clinical Research Unit Pitié Salpêtrière - Charles Foix, CHU La Pitié-Salpêtrière - APHP

Official's Role

Study Director

Facility Information:

Facility Name

Infectious diseases department, Raymond-Poincaré Hospital - APHP

City

Garches

ZIP/Postal Code

92380

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

33773631

Citation

Dinh A, Ropers J, Duran C, Davido B, Deconinck L, Matt M, Senard O, Lagrange A, Makhloufi S, Mellon G, de Lastours V, Bouchand F, Mathieu E, Kahn JE, Rouveix E, Grenet J, Dumoulin J, Chinet T, Pepin M, Delcey V, Diamantis S, Benhamou D, Vitrat V, Dombret MC, Renaud B, Perronne C, Claessens YE, Labarere J, Bedos JP, Aegerter P, Cremieux AC; Pneumonia Short Treatment (PTC) Study Group. Discontinuing beta-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial. Lancet. 2021 Mar 27;397(10280):1195-1203. doi: 10.1016/S0140-6736(21)00313-5. Erratum In: Lancet. 2021 Jun 5;397(10290):2150.

Results Reference

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Customized Antibiotic Treatment Duration Among Hospitalized Patients With Moderately Severe Community-Acquired Pneumonia

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