Combined Use of a Respiratory Broad Panel Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Hospitalized Sickle-cell Adults With Acute Chest Syndrome. (Antibio_STA)

Combined Use of a Respiratory Broad Panel Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Adult Patients With Sickle-cell Disease Hospitalized for Acute Chest Syndrome. A Bi-centric, Open, Parallel-group, Randomized Controlled Study

Many patients with Sickle Cell Disease (SCD) may develop Acute Chest Syndrome (ACS). ACS is usually caused by a Lower respiratory tract infection (LRTI) which may be caused by either a bacterium or a virus. Antibiotics are usually used for 7 to 10 days with no microbiological workup.

The hypothesis of the study is that the identification of the microorganisms might lead to a reduction of antibiotics exposure and a better care of the patients.

We speculate that an early pathogen-directed strategy (respiratory broad panel multiplex PCR and early antibiotics interruption based on the PCT values decrease) might reduce the antibiotics exposure in SCD patients with ACS who are hospitalized and for whom an antibiotic treatment is indicated, as compared with usual care

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Acute Chest Syndrome
• Intervention / Treatment: Procedure: Control: usual antibiotic treatment; Procedure: Intervention: Combined use of a respiratory broad panel multiplex PCR and procalcitonin

Detailed Description

Acute Chest Syndrome (ACS) is a frequent and severe acute complication of sickle-cell disease. It may affect 10 to 20% of hospitalized patients and is the leading cause of death. The symptoms combine a new pulmonary infiltrate and symptom(s) among fever, cough, dyspnea, expectoration, chest pain and crackles. The pathophysiology of ACS is complex and there are many interlinked aetiologies.

Lower respiratory tract infection (LRTI) is one of the most frequent aetiologies of ACS. Intracellular bacteria (Chlamydia, Mycoplasma), respiratory virus (especially respiratory syncytial virus) and pyogenes (Streptococcus pneumoniae and Staphylococcus aureus) are the most frequently identified microorganisms. Nevertheless, the clinical presentation of ACS is not helpful for the diagnosis of LRTI; the respiratory tract samples are not always collected, either because the patients do not expectorate or because the benefit-risk ratio of a fiberoptic bronchoscopy may be not advantageous. Moreover, usual diagnostic test are not enough performant.

The current practices rely on the systematic administration of antibiotics for 7 to 10 days. The efficacy and safety of alternative diagnostic and therapeutic strategies have never been evaluated in controlled clinical trial to cure ACS.

In this context, the optimisation of the microbiological documentation of ACS might enhance the use of antimicrobial drugs, reduce their duration, and limit the emergence of multidrug resistant bacteria.

Therefore, we speculate that an early pathogen-directed strategy (respiratory broad panel multiplex PCR and early antibiotics interruption based on the PCT values decrease) might reduce the antibiotics exposure in SCD patients with ACS who are hospitalized and for whom an antibiotic treatment is indicated, as compared with usual care.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Muriel FARTOUKH, PU-PH; Phone Number: 01 56 01 65 74; Email: muriel.fartoukh@aphp.fr
• Study Contact Backup: Name: Guillaume VOIRIOT, MD; Phone Number: 01 56 01 65 74; Email: guillaume.voiriot@aphp.fr

Study Locations

• France
  • Paris, France, 75020
    • Service de Réanimation et USC médico-chirurgicale

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Sickle Cell Disease patients with ACS with an antibiotic therapy indication
• Signed and informed consent
• Affiliated with social security

Exclusion Criteria:

Documented extra-pulmonary bacterial infection at the time of inclusion;

• Patients who received antibiotics for more than 24 hours before the diagnosis of ACS (during the primary hospitalization)
• Known severe immunosuppression (AIDS, neutropenia (<1000 PNN), hematology, solid tumor under chemotherapy, transplanted organ); long-term treatment with hydroxy-carbamide is not considered
• Pregnant or lactating women;
• Person deprived of liberty or under legal protection;
• Participation in another interventional study of type Jardé 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control; usual antibiotic treatment	Procedure: Control: usual antibiotic treatment; usual antibiotic treatment
Experimental: Intervention; targeted antibiotic treatment according to the results of PCR multiplex	Procedure: Intervention: Combined use of a respiratory broad panel multiplex PCR and procalcitonin; The actions or procedures added by the research are the realization of a nasopharyngeal swab in the two strategies, and the PCT assay at D1, D3 and D7 in the pathogen-directed strategy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
to compare the antibiotics exposure at 28 days (D28) after the diagnosis of ACS between the two strategies	Day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of microbiological documentation of ACS	Day 28
Survival at 28 days	Day 28
occurrence of a secondary bacterial respiratory infection or any other secondary infection at 28 days	Day 28
transfusion and exchange transfusion at 28 days	Day 28
ICU and hospital lengths of stay	Day 28
Readmission rate in hospital at 28 days	Day 28
Transfer to ICU at 28 days (D28) after the diagnosis of ACS between the two strategies	Day 28
Global use of antibiotics at 28 days	Day 28
Time to clinical stability at 28 days	Day 28

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Muriel FARTOUKH, PU-PH, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Actual): October 10, 2022
• Study Completion (Actual): October 10, 2022

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: SCD; antibiotic treatment; Acute chest syndrome; PCR multiplex
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Syndrome; Anemia, Sickle Cell; Acute Chest Syndrome; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: APHP180159

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No