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

Sickle Cell Disease Clinical Trial

— Antibio_STA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03919266
• Other study ID #: APHP180159
• Status: Completed
• Phase: N/A
• Start date: June 2, 2020
• Est. completion date: October 10, 2022

Study information

• Verified date: June 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: October 10, 2022
• Est. primary completion date: October 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Chest Syndrome
• Anemia, Sickle Cell
• Sickle Cell Disease
• Syndrome

Intervention

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
• Control: usual antibiotic treatment
usual antibiotic treatment

Locations

Country	Name	City	State
France	Service de Réanimation et USC médico-chirurgicale	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

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