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 hypothesize 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
Condition or disease | Intervention/treatment | Phase |
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Acute Chest Syndrome Sickle Cell Disease | Procedure: Intervention: Combined use of a respiratory broad panel multiplex PCR and procalcitonin Procedure: Control: usual antibiotic treatment | Not Applicable |
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 benefice-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 security 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 (Clinical Trial) |
Estimated Enrollment : | 72 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | June 2, 2020 |
Estimated Primary Completion Date : | July 2021 |
Estimated Study Completion Date : | July 2021 |
Arm | Intervention/treatment |
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Control
usual antibiotic treatment
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Procedure: Control: usual antibiotic treatment
usual antibiotic treatment
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Experimental: Intervention
targeted antibiotic treatment according to the results of PCR multiplex
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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
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Documented extra-pulmonary bacterial infection at the time of inclusion;
Contact: Muriel FARTOUKH, PU-PH | 01 56 01 65 74 | muriel.fartoukh@aphp.fr | |
Contact: Guillaume VOIRIOT, MD | 01 56 01 65 74 | guillaume.voiriot@aphp.fr |
France | |
Service de Réanimation et USC médico-chirurgicale | Recruiting |
Paris, France, 75020 | |
Contact: Muriel FARTOUKH, PU-PH 01 56 01 65 74 muriel.fartoukh@aphp.fr | |
Contact: Guillaume VOIRIOT, MD 01 56 01 65 74 guillaume.voiriot@aphp.fr |
Principal Investigator: | Muriel FARTOUKH, PU-PH | Assistance Publique - Hôpitaux de Paris |
Tracking Information | |||||||||
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First Submitted Date ICMJE | April 15, 2019 | ||||||||
First Posted Date ICMJE | April 18, 2019 | ||||||||
Last Update Posted Date | February 17, 2021 | ||||||||
Actual Study Start Date ICMJE | June 2, 2020 | ||||||||
Estimated Primary Completion Date | July 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
to compare the antibiotics exposure at 28 days (D28) after the diagnosis of ACS between the two strategies [ Time Frame: Day 28 ] | ||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Combined Use of a Respiratory Broad Panel Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Hospitalized Sickle-cell Adults With Acute Chest Syndrome. | ||||||||
Official Title ICMJE | 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 | ||||||||
Brief 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 hypothesize 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 |
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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 benefice-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 security 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. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Not Applicable | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
72 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | July 2021 | ||||||||
Estimated Primary Completion Date | July 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria: Documented extra-pulmonary bacterial infection at the time of inclusion;
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | France | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03919266 | ||||||||
Other Study ID Numbers ICMJE | APHP180159 | ||||||||
Has Data Monitoring Committee | No | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Assistance Publique - Hôpitaux de Paris | ||||||||
Study Sponsor ICMJE | Assistance Publique - Hôpitaux de Paris | ||||||||
Collaborators ICMJE | Not Provided | ||||||||
Investigators ICMJE |
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PRS Account | Assistance Publique - Hôpitaux de Paris | ||||||||
Verification Date | February 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |