Pneumocystis Pneumonia Diagnosis in HIV- Patients (PNEUMOQUANT)

Pneumocystis Pneumonia Diagnosis in HIV- Patients: Assessment of the Real Time Polymerase Chain Reaction Quantification on Oropharyngeal Rinse

Pneumocystis jirovecii pneumonia is a serious and frequent infection in immunocompromised patients, whose evolution is potentially fatal if untreated. It is the most common opportunistic infections classifying patients infected with human immunodeficiency virus (human immunodeficiency virus +) at the stage acquired immune deficiency syndrome. Data from the french Institute for Health Watch showed in 2011 that 31% of 1400 cases of acquired immune deficiency syndrome were revealed by Pneumocystis jirovecii pneumonia.

Pneumocystis jirovecii pneumonia also increasingly concerns immunocompromised human immunodeficiency virus negative patients, due to the increasing use of immunosuppressive therapies (including corticosteroids), of anticancer cytostatics and biotherapies, in the context of grafts, transplants, but also from autoimmune or inflammatory chronic diseases.

Recent data show that the number of cases occurring in patients Pneumocystis jirovecii pneumonia human immunodeficiency virus - in France is now higher than the cases occurring in Pneumocystis jirovecii pneumonia +. The severity of the Pneumocystis jirovecii pneumonia is increased in patients with human immunodeficiency virus -, in whom the evolution is faster, with mechanical ventilation often required and higher mortality, requiring a fast and early diagnosis. Routine diagnosis relies on the detection of the fungus in the bronchoalveolar lavage, using stains (May Grunwald Giemsa or immunofluorescence) and Polymerase Chain Reaction. Polymerase Chain Reaction provides a diagnostic gain in immunocompromised patients not infected with human immunodeficiency virus that may present a pejorative table quickly despite low fungal burden. However, the deoxyribonucleic acid of the fungus can sometimes be detected in the absence of scalable Pneumocystis jirovecii pneumonia, and then shows a pulmonary colonization by Pneumocystis jirovecii. It is therefore important to improve the positive predictive value of Pneumocystis Polymerase Chain Reaction, to guide the management of optimal patient.

In this work, the investigators propose to evaluate the Polymerase Chain Reaction on oropharyngeal rinse, non-invasive sampling and therefore probably less often positive and specific active infection. The investigators will develop a quantitative Polymerase Chain Reaction to identify a fungal load threshold number of copies / mL for diagnosing Pneumocystis jirovecii pneumonia with better positive predictive value.

Study Overview

• Status: Recruiting
• Conditions: Pneumonia, Pneumocystis
• Intervention / Treatment: Other: Polymerase Chain Reaction on Oropharyngeal rinse

• Study Type: Interventional
• Enrollment (Anticipated): 1250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Florence Robert-Gangneux, Md, PhD; Email: florence.robertgangneux@chu-rennes.fr
• Study Contact Backup: Name: Anne Ganivet; Email: anne.ganivet@chu-rennes.fr

Study Locations

• France
  • Amiens, France, 80000
    • Recruiting
    • CHU Amiens
    • Principal Investigator: Anne Totet, MD, PhD
    • Sub-Investigator: Vincent Jounieaux, MD, PhD
    • Sub-Investigator: Jean-Luc Schmit, MD, PhD
  • Brest, France, 29200
    • Recruiting
    • CHU Brest
    • Principal Investigator: Gilles Nevez, MD-PhD
    • Sub-Investigator: Francis Couturaud, MD-PhD
    • Sub-Investigator: Séverine Ansart, MD-PhD
  • Rennes, France, 35000
    • Recruiting
    • CHU Rennes
    • Sub-Investigator: Jean-Pierre Gangneux, MD, PhD
    • Sub-Investigator: Yves Le Tulzo, MD, PhD
    • Sub-Investigator: Stéphane Jouneau, MD, PhD
    • Sub-Investigator: Pierre Tattevin, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age over 18 years
• Clinical or radiological indication for a broncho-alveolar lavage to search infectious agents including Pneumocystis jirovecii
• Patients with risk factors for developing a Pneumocystis jirovecii pneumonia : underlying malignancy (solid cancer, hematologic disease), organ transplant or hematopoietic stem cells, autoimmune disease or chronic inflammatory disease justifying immunosuppressive therapy (chemotherapy anticancer, immunomodulatory, biotherapy, corticosteroids) or patient treated with corticosteroids for more than a month or congenital immune deficiency or other causes of immunosuppression (excluding human immunodeficiency virus) at the discretion of the clinician,
• Informed consent given.

Exclusion Criteria:

• Patient human immunodeficiency virus positive
• Contraindication to the achievement of broncho-alveolar lavage,
• Contraindication to the achievement of a Oropharyngeal rinse (disorder of consciousness, swallowing disorder),
• Prophylaxis with cotrimoxazole or aerosol pentamidine,
• Empirical curative treatment with cotrimoxazole or other curative therapeutic alternative (pentamidine, atovaquone, dapsone, clindamycin-primaquine) started for more than 48 hours,
• Major person under legal protection (backup justice, trusteeship, guardianship), person deprived of liberty.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Oropharyngeal rinse; Polymerase Chain Reaction on Oropharyngeal rinse: Dosage of Pneumocystis jiroveci will be performed on the broncho-alveolar lavage following the usual routine diagnosis. Polymerase Chain Reaction will be performed on the broncho-alveolar lavage and the oropharyngeal rinse (not communicated to the clinician result) in the same series, in order to compare the results of the fungal quantification.

Other: Polymerase Chain Reaction on Oropharyngeal rinse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Predictive Value of Polymerase Chain Reaction on oropharyngeal rinse	Definition of a numerical threshold from a multivariate analysis, for positioning the result of this test in combination with other clinical or laboratory parameters.	At the end of inclusion period (24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Broncho-alveolar lavage Standardization	Definition of a quantitative threshold (number of copies / mL) for the interpretation of the Polymerase Chain Reaction on the broncho-alveolar lavage to estimate at best positive predictive value of Pneumocystis Polymerase Chain Reaction	At the end of inclusion period (24 months)
Evaluation of serum dosage of β-1,3-D glucan	Definition of a positivity threshold to evoke a certain Pneumocystis jirovecii pneumonia, alone or in combination with Polymerase Chain Reaction.	At the end of inclusion period (24 months)
Prevalence of genetic mutations of pneumocystis jirovecii	Analysis of the prevalence of mutations in the gene encoding the synthase dihydropteroate Pneumocystis jirovecii in patients with Pneumocystis jirovecii pneumonia or colonized and comparison with previous calculations Brittany and Picardy régions using a parametric test (t test) or nonparametric (Mann-test Whitney)	At the end of inclusion period (24 months)

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Study Director: Florence Robert-Gangneux, Md, PhD, CHU Rennes

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): August 1, 2024

Study Registration Dates

• First Submitted: January 5, 2016
• First Submitted That Met QC Criteria: January 6, 2016
• First Posted (Estimate): January 7, 2016

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Polymerase Chain Reaction; Pneumocystis jirovecii; Oropharyngeal Rinse
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections and Mycoses; Mycoses; Lung Diseases, Fungal; Pneumocystis Infections; Pneumonia; Pneumonia, Pneumocystis
• Other Study ID Numbers: 2015-A00408-41; 35RC14_9890 (Other Identifier: Other Identifier)