Description of Pneumococcal Pneumonia

NCT03322670 | Completed

• 1 other identifier: N° ID RCB : 2016-A01537-44
• Study Type: observational
• Target: 412
• Locations: 1 country
• Sites: 1

Brief Summary

Statement of the problem: Overprescription of antibiotics raises important public health issues because of the emergence of multiresistant bacteria by selection pressure. The results of the observational prospective study entitled "CAPA" on the description of 886 suspected cases of acute community-acquired pneumonia (CAP) treated in general practices in France confirm that, whatever the etiologic hypothesis and the results of the chest X-ray, these patients routinely receive antibiotics. Therefore, it is important to be able to distinguish cases of pneumococcal CAP in which early antibiotic treatment is justified from those cases for which another strategy could be considered. Primary objective: To identify the clinical, biological and radiological characteristics of patients with pneumococcal CAP amongst all patients with CAP radiologically confirmed, in general practice in France. Design : Prospective cross-sectional descriptive study. Inclusion criteria. Adults older than 18 showing clinical signs suggestive of CAP (at least one sign of infection and at least one pulmonary sign) and able to realize chest X ray within 6 hours after prescription. Patient follow-up procedures. Patients will be treated by standard of care according to French recommendations. After observing clinical signs suggestive of CAP, the physician prescribes a chest X-ray. Then, protocol-specific examinations (blood sample, oropharyngeal sample for multiplex polymerase chain reaction (PCR), sputum sample testing (induced expectoration if possible), urinary sample) will be performed on all out patients. Patients will be contacted again on day 28 to increase diagnostic certainty. For patients with clinical signs of CAP and hospitalized, the investigator will ask their consent to retrieve the hospital report, on or before day 28 and to be contacted on day 90.

Conditions

Community-acquired Pneumonia

Keywords

community-acquired pneumonia; family practice; streptococcus pneumoniae

Outcome Measures

Primary Outcomes (1)

• Percentage of pneumococcal CAP amongst the other etiological CAP with a positive chest X-ray

  Determination oh the proportion of pneumococcal CAP among all CAP radiologically confirmed with other etiologies identified, followed in general practice in France. Comparison of the clinical, biological and radiological characteristics of patients with radiologically confirmed pneumococcal CAP to those with radiologically confirmed CAP patients for whom another microbiological etiology was identified

  Day 0

Secondary Outcomes (1)

• Description of clinical characteristics of patients treated in general practice for a radiologically confirmed CAP, based on the microbiological etiologies

  Day 0

Other Outcomes (7)

• Description of biological characteristics of patients treated in general practice for a radiologically confirmed CAP, based on the microbiological etiologies

  Day 0

• Description radiological characteristics of patients treated in general practice for a radiologically confirmed CAP, based on all the microbiological etiologies.

  day 0

• Incidence rate of pneumococcal CAP radiologically confirmed on chest X-ray, in the general practitioners settings

  Day 0

Study Arms (5)

Signs of CAP and a positive chest X-Ray

Patients with at least 2 signs suggestive of CAP on presentation at general practice (one general sign of infection and one sign of pulmonary localization) and and a chest X-Ray not compatible with CAP

Other: Signs of CAP and a positive chest X-Ray

Patients directly hospitalized

Patients with at least 2 signs suggestive of CAP on presentation at general practice (one general sign of infection and one sign of pulmonary localization) and and who are directly hospitalized before complementary examinations

Other: Patients directly hospitalized

Control patients

Healthy Patients (age-matched with a radiologically confirmed CAP patient)

Diagnostic Test: Control patients

Patients with partial participation

Patients with at least 2 signs suggestive of CAP on presentation at general practice (one general sign of infection and one sign of pulmonary localization) and who can not or do not want to perform all the complementary examinations of the study

Other: Patients with partial participation

Signs of CAP and a negative Chest X-Ray

Patients with at least 2 signs suggestive of CAP on presentation at general practice (one general sign of infection and one sign of pulmonary localization) and and a chest X-Ray not compatible with CAP

Other: Signs of CAP and a negative chest X-Ray

Interventions

Signs of CAP and a positive chest X-Ray OTHER

* collection of clinical examination data * biological and bacteriological examinations (blood, urine, sputum, nasopharyngeal) * self-reported questionnaires on duration of symptoms and restriction of activity * telephone contact on day 28 and day 90 if hospitalized before day 28

Signs of CAP and a positive chest X-Ray

Patients directly hospitalized OTHER

* collection of clinical examination data * telephone contact on day 28 and retrieval of hospitalization report * telephone contact on day 90

Patients directly hospitalized

Control patients DIAGNOSTIC_TEST

\- bacteriological examinations (urine)

Control patients

Patients with partial participation OTHER

\- collection of clinical examination data

Patients with partial participation

Signs of CAP and a negative chest X-Ray OTHER

* collection of clinical examination data * telephone contact on day 28

Signs of CAP and a negative Chest X-Ray

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

In France, patients who visit a General Practitioner and who have clinical signs suggestive of CAP at clinic visits. For the control cohort, healthy patient who visit a General Practitioner in the two weeks following the inclusion of a patient with CAP confirmed on the chest X-ray

You may qualify if:

• Age ≥18 years
• Presence of at least 2 signs suggestive of CAP on presentation at general practice (one general sign of infection and one sign of pulmonary localization):
• at least one sign of infection
• fever \> 38.5°C (maximum temperature measured by the patient or GP)
• tachycardia \> 100 /min
• hyperpnea \> 20/min
• global impression of severity\*
• muscle aches, fatigue, or chills
• and at least one sign of pulmonary localization
• cough
• unilateral chest pain
• purulent or non-purulent sputum
• auscultatory abnormality compatible with CAP (focus of crackles)
• Affiliation with health insurance system
• Chest X-ray performed within 6 hours of presenting to the general practice

You may not qualify if:

• conditions of medical treatment not allowing for chest X-ray within 6 hours after diagnosis of CAP
• contraindication to chest X-ray
• conditions of medical management not allowing the realization of biological and bacteriological examinations within 8 hours of D0 consultation (except for patient immediately hospitalized)
• chest X-ray finding not compatible with CAP : chest X-ray showing another lung disease than a CAP (for example: pulmonary neoplasia, tuberculosis, pulmonary embolism)
• Patients presenting with any of the following will not be included in the study:
• Patients who are investigational site staff members or relatives of those site staff member or subjects who are Pfizer employees directly involved in the conduct of the trial.
• Patients with suspicion of CAP or other respiratory infectious diseases, as well as evidence of or documented concomitant infectious disease.
• Patients residing in any long-term care facilities (for example, nursing homes, respite care facilities, etc).
• Patients with known bronchial obstruction or a history of post-obstructive pneumonia. Chronic obstructive pulmonary disease (COPD) is permissible, provided there has not been an exacerbation within the 3 months prior to enrollment.
• Patients with primary lung cancer or another malignancy metastatic to the lungs.
• Patients with fever (measured temperature of ≥38.0° C measured by a healthcare provider).
• Patients with significant immunosuppressive disease such as AIDS, leukemia, etc.
• Patients with either pneumococcal conjugate vaccine (PCV) and/or pneumococcal polysaccharide vaccine (PPV) administration within the past 30 days.

Sponsors & Collaborators

• CNGE Conseil: lead

Study Sites (1)

URC-CIC Paris Descartes-Cochin-Necker

Paris, 75006, France

Location

Related Publications (30)

• Hosker H, Cooke NJ, Hawkey P. Antibiotics in chronic obstructive pulmonary disease. BMJ. 1994 Apr 2;308(6933):871-2. doi: 10.1136/bmj.308.6933.871. No abstract available.

  PMID: 8173363 BACKGROUND

• Wipf JE, Lipsky BA, Hirschmann JV, Boyko EJ, Takasugi J, Peugeot RL, Davis CL. Diagnosing pneumonia by physical examination: relevant or relic? Arch Intern Med. 1999 May 24;159(10):1082-7. doi: 10.1001/archinte.159.10.1082.

  PMID: 10335685 BACKGROUND

• Jackson ML, Neuzil KM, Thompson WW, Shay DK, Yu O, Hanson CA, Jackson LA. The burden of community-acquired pneumonia in seniors: results of a population-based study. Clin Infect Dis. 2004 Dec 1;39(11):1642-50. doi: 10.1086/425615. Epub 2004 Nov 8.

  PMID: 15578365 BACKGROUND

• Holm A, Nexoe J, Bistrup LA, Pedersen SS, Obel N, Nielsen LP, Pedersen C. Aetiology and prediction of pneumonia in lower respiratory tract infection in primary care. Br J Gen Pract. 2007 Jul;57(540):547-54.

  PMID: 17727747 BACKGROUND

• Porath A, Schlaeffer F, Lieberman D. The epidemiology of community-acquired pneumonia among hospitalized adults. J Infect. 1997 Jan;34(1):41-8. doi: 10.1016/s0163-4453(97)80008-4.

  PMID: 9120323 BACKGROUND

• Said MA, Johnson HL, Nonyane BA, Deloria-Knoll M, O'Brien KL; AGEDD Adult Pneumococcal Burden Study Team; Andreo F, Beovic B, Blanco S, Boersma WG, Boulware DR, Butler JC, Carratala J, Chang FY, Charles PG, Diaz AA, Dominguez J, Ehara N, Endeman H, Falco V, Falguera M, Fukushima K, Garcia-Vidal C, Genne D, Guchev IA, Gutierrez F, Hernes SS, Hoepelman AI, Hohenthal U, Johansson N, Kolek V, Kozlov RS, Lauderdale TL, Marekovic I, Masia M, Matta MA, Miro O, Murdoch DR, Nuermberger E, Paolini R, Perello R, Snijders D, Plecko V, Sorde R, Stralin K, van der Eerden MM, Vila-Corcoles A, Watt JP. Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques. PLoS One. 2013;8(4):e60273. doi: 10.1371/journal.pone.0060273. Epub 2013 Apr 2.

  PMID: 23565216 BACKGROUND

• Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014 Oct 23;371(17):1619-28. doi: 10.1056/NEJMra1312885. No abstract available.

  PMID: 25337751 BACKGROUND

• Dorca J, Torres A. Lower respiratory tract infections in the community: towards a more rational approach. Eur Respir J. 1996 Aug;9(8):1588-9. doi: 10.1183/09031936.96.09081588. No abstract available.

  PMID: 8866576 BACKGROUND

• Gennis P, Gallagher J, Falvo C, Baker S, Than W. Clinical criteria for the detection of pneumonia in adults: guidelines for ordering chest roentgenograms in the emergency department. J Emerg Med. 1989 May-Jun;7(3):263-8. doi: 10.1016/0736-4679(89)90358-2.

  PMID: 2745948 BACKGROUND

• Metlay JP, Fine MJ. Testing strategies in the initial management of patients with community-acquired pneumonia. Ann Intern Med. 2003 Jan 21;138(2):109-18. doi: 10.7326/0003-4819-138-2-200301210-00012.

  PMID: 12529093 BACKGROUND

• Partouche H, Buffel du Vaure C, Personne V, Le Cossec C, Garcin C, Lorenzo A, Ghasarossian C, Landais P, Toubiana L, Gilberg S. Suspected community-acquired pneumonia in an ambulatory setting (CAPA): a French prospective observational cohort study in general practice. NPJ Prim Care Respir Med. 2015 Mar 12;25:15010. doi: 10.1038/npjpcrm.2015.10.

  PMID: 25763466 BACKGROUND

• Young M, Marrie TJ. Interobserver variability in the interpretation of chest roentgenograms of patients with possible pneumonia. Arch Intern Med. 1994 Dec 12-26;154(23):2729-32. doi: 10.1001/archinte.1994.00420230122014.

  PMID: 7993157 BACKGROUND

• Claessens YE, Debray MP, Tubach F, Brun AL, Rammaert B, Hausfater P, Naccache JM, Ray P, Choquet C, Carette MF, Mayaud C, Leport C, Duval X. Early Chest Computed Tomography Scan to Assist Diagnosis and Guide Treatment Decision for Suspected Community-acquired Pneumonia. Am J Respir Crit Care Med. 2015 Oct 15;192(8):974-82. doi: 10.1164/rccm.201501-0017OC.

  PMID: 26168322 BACKGROUND

• Ortqvist A, Hedlund J, Wretlind B, Carlstrom A, Kalin M. Diagnostic and prognostic value of interleukin-6 and C-reactive protein in community-acquired pneumonia. Scand J Infect Dis. 1995;27(5):457-62. doi: 10.3109/00365549509047046.

  PMID: 8588135 BACKGROUND

• Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004 Feb 21;363(9409):600-7. doi: 10.1016/S0140-6736(04)15591-8.

  PMID: 14987884 BACKGROUND

• Le Bel J, Hausfater P, Chenevier-Gobeaux C, Blanc FX, Benjoar M, Ficko C, Ray P, Choquet C, Duval X, Claessens YE; ESCAPED study group. Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan. Crit Care. 2015 Oct 16;19:366. doi: 10.1186/s13054-015-1083-6.

  PMID: 26472401 BACKGROUND

• van Vugt SF, Broekhuizen BD, Lammens C, Zuithoff NP, de Jong PA, Coenen S, Ieven M, Butler CC, Goossens H, Little P, Verheij TJ; GRACE consortium. Use of serum C reactive protein and procalcitonin concentrations in addition to symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough: diagnostic study. BMJ. 2013 Apr 30;346:f2450. doi: 10.1136/bmj.f2450.

  PMID: 23633005 BACKGROUND

• van der Meer V, Neven AK, van den Broek PJ, Assendelft WJ. Diagnostic value of C reactive protein in infections of the lower respiratory tract: systematic review. BMJ. 2005 Jul 2;331(7507):26. doi: 10.1136/bmj.38483.478183.EB. Epub 2005 Jun 24.

  PMID: 15979984 BACKGROUND

• Holm A, Pedersen SS, Nexoe J, Obel N, Nielsen LP, Koldkjaer O, Pedersen C. Procalcitonin versus C-reactive protein for predicting pneumonia in adults with lower respiratory tract infection in primary care. Br J Gen Pract. 2007 Jul;57(540):555-60.

  PMID: 17727748 BACKGROUND

• Niederman MS. Biological markers to determine eligibility in trials for community-acquired pneumonia: a focus on procalcitonin. Clin Infect Dis. 2008 Dec 1;47 Suppl 3:S127-32. doi: 10.1086/591393.

  PMID: 18986278 BACKGROUND

• Melbye H, Stocks N. Point of care testing for C-reactive protein - a new path for Australian GPs? Aust Fam Physician. 2006 Jul;35(7):513-7.

  PMID: 16820825 BACKGROUND

• Christ-Crain M, Muller B. Procalcitonin and pneumonia: is it a useful marker? Curr Infect Dis Rep. 2007 May;9(3):233-40. doi: 10.1007/s11908-007-0037-9.

  PMID: 17430706 BACKGROUND

• Roson B, Fernandez-Sabe N, Carratala J, Verdaguer R, Dorca J, Manresa F, Gudiol F. Contribution of a urinary antigen assay (Binax NOW) to the early diagnosis of pneumococcal pneumonia. Clin Infect Dis. 2004 Jan 15;38(2):222-6. doi: 10.1086/380639. Epub 2003 Dec 18.

  PMID: 14699454 BACKGROUND

• Guchev IA, Yu VL, Sinopalnikov A, Klochkov OI, Kozlov RS, Stratchounski LS. Management of nonsevere pneumonia in military trainees with the urinary antigen test for Streptococcus pneumoniae: an innovative approach to targeted therapy. Clin Infect Dis. 2005 Jun 1;40(11):1608-16. doi: 10.1086/429919. Epub 2005 May 2.

  PMID: 15889358 BACKGROUND

• Song JY, Eun BW, Nahm MH. Diagnosis of pneumococcal pneumonia: current pitfalls and the way forward. Infect Chemother. 2013 Dec;45(4):351-66. doi: 10.3947/ic.2013.45.4.351. Epub 2013 Dec 27.

  PMID: 24475349 BACKGROUND

• Pride MW, Huijts SM, Wu K, Souza V, Passador S, Tinder C, Song E, Elfassy A, McNeil L, Menton R, French R, Callahan J, Webber C, Gruber WC, Bonten MJ, Jansen KU. Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine. Clin Vaccine Immunol. 2012 Aug;19(8):1131-41. doi: 10.1128/CVI.00064-12. Epub 2012 Jun 6.

  PMID: 22675155 BACKGROUND

• Reddington K, Tuite N, Barry T, O'Grady J, Zumla A. Advances in multiparametric molecular diagnostics technologies for respiratory tract infections. Curr Opin Pulm Med. 2013 May;19(3):298-304. doi: 10.1097/MCP.0b013e32835f1b32.

  PMID: 23425918 BACKGROUND

• Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L; CDC EPIC Study Team. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015 Jul 30;373(5):415-27. doi: 10.1056/NEJMoa1500245. Epub 2015 Jul 14.

  PMID: 26172429 BACKGROUND

• Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med. 2004 Mar 22;164(6):637-44. doi: 10.1001/archinte.164.6.637.

  PMID: 15037492 BACKGROUND

• Flamaing J, De Backer W, Van Laethem Y, Heijmans S, Mignon A. Pneumococcal lower respiratory tract infections in adults: an observational case-control study in primary care in Belgium. BMC Fam Pract. 2015 May 27;16:66. doi: 10.1186/s12875-015-0282-1.

  PMID: 26012956 BACKGROUND

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITHOUT DNA

* Blood: * Blood count * CRP * Procalcitonin (PCT) * Blood cultures * Oropharynx: \- Oropharyngeal sample: for multiplex polymerase chain reaction (PCR) * Sputum: \- Sputum sample testing (induced expectoration if possible) * Urine: * Pneumococcal urinary antigen test (Alere BinaxNOW) * Luminex technology-based multiplex urine antigen detection (UAD) * Urine collection (for urine bank at Central Laboratory)

MeSH Terms

Conditions

Community-Acquired Pneumonia

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases

Study Officials

• Serge Gilberg, Professor

  University Paris Descartes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Family practice

Study Record Dates

• First Submitted: September 25, 2017
• First Posted: October 26, 2017
• Study Start: December 21, 2017
• Primary Completion: December 6, 2019
• Study Completion: January 3, 2020
• Last Updated: February 12, 2021

Record last verified: 2021-02

Locations

FR (1)