Shortened Antibiotic Treatment of 5 Days in Community-Acquired Pneumonia

Community-acquired Pneumonia Clinical Trial

— CAP5  

Official title:

Shortened Antibiotic Treatment in Community-Acquired Pneumonia: A Nationwide Danish Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04089787
• Other study ID #: H-19014479
• Secondary ID: 2019-000404-15
• Status: Recruiting
• Phase: Phase 4
• Start date: September 18, 2019
• Est. completion date: June 1, 2024

Study information

• Verified date: March 2023
• Source: Hvidovre University Hospital
• Contact: Simone Bastrup Israelsen, MD
• Phone: +45 40335495
• Email: simone.elisabeth.bastrup.israelsen.02[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CAP5 is an investigator-initiated multicentre non-inferiority randomized controlled trial which aims to assess the efficacy and safety of shortened antibiotic treatment duration of community-acquired pneumonia (CAP) in hospitalized adult patients based on clinical stability criteria. Five days after initiation of antimicrobial therapy for CAP, participants are randomized 1:1 to parallel treatment arms: 5 days (intervention) or minimum 7 days (control) of antibiotic treatment. The intervention group discontinues antibiotics at day 5 if clinically stable and afebrile for at least 48 hours. The control group receives antibiotics for a duration of 7 days or longer at the discretion of the treating physician. The primary outcome is 90-day readmission-free survival which will be tested with a non-inferiority margin of 6%.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 564
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Hospitalized with community-acquired pneumonia; defined as new pulmonary infiltrate on chest X-ray and at least one symptom compatible with pneumonia (cough, fever, dyspnoea and/or chest pain)
• Initiation of antibiotics within 12 hours of the time of the chest X-ray with an infiltrate
• Age = 18 years
• Afebrile (temperature = 37.8 °C) for 48 hours at randomization
• Clinically stable at randomization (systolic blood pressure = 90 mm Hg, heart rate = 100/min., respiratory rate = 24/min., peripheral oxygen saturation = 90%)

Exclusion Criteria:

• Immunosuppression (HIV-positive, neutropenia, corticosteroid treatment (=10 mg/day of prednisone or the equivalent for >30 days), chemotherapy, immunosuppressive agents, immunosuppressed after solid organ transplantation, asplenia)
• Hospitalization during the previous 14 days
• Antibiotic treatment (>2 days) within the past 30 days
• Uncommon cause requiring longer duration of antimicrobial therapy (Pseudomonas aeruginosa, Staphylococcus aureus, Mycobacterium spp., fungi)
• Extrapulmonary infection (e.g. endocarditis, meningitis, or abscess)
• Pleural empyema or lung abscess
• Pleural effusion requiring drainage tube
• Intensive care unit (ICU) admittance
• Pregnancy and breastfeeding

Related Conditions & MeSH terms

• Community-acquired Pneumonia
• Pneumonia

Intervention

Other:
• Intervention
Shortened antibiotic treatment of 5 days
• Control
Antibiotic treatment of 7 days or longer at the discretion of the treating physician

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Gentofte Hospital	Gentofte
Denmark	Herlev Hospital	Herlev
Denmark	Nordsjællands Hospital	Hillerød
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Odense University Hospital	Odense

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Benfield

Country where clinical trial is conducted

Denmark, 

References & Publications (24)

Aliberti S, Blasi F, Zanaboni AM, Peyrani P, Tarsia P, Gaito S, Ramirez JA. Duration of antibiotic therapy in hospitalised patients with community-acquired pneumonia. Eur Respir J. 2010 Jul;36(1):128-34. doi: 10.1183/09031936.00130909. Epub 2009 Nov 19. — View Citation

Aliberti S, Ramirez J, Giuliani F, Wiemken T, Sotgiu G, Tedeschi S, Carugati M, Valenti V, Marchioni M, Camera M, Piro R, Del Forno M, Milani G, Faverio P, Richeldi L, Deotto M, Villani M, Voza A, Tobaldini E, Bernardi M, Bellone A, Bassetti M, Blasi F. Individualizing duration of antibiotic therapy in community-acquired pneumonia. Pulm Pharmacol Ther. 2017 Aug;45:191-201. doi: 10.1016/j.pupt.2017.06.008. Epub 2017 Jun 27. — View Citation

Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P, Perrin D, Fieux F, Aubas S; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003 Nov 19;290(19):2588-98. doi: 10.1001/jama.290.19.2588. — View Citation

Choudhury G, Mandal P, Singanayagam A, Akram AR, Chalmers JD, Hill AT. Seven-day antibiotic courses have similar efficacy to prolonged courses in severe community-acquired pneumonia--a propensity-adjusted analysis. Clin Microbiol Infect. 2011 Dec;17(12):1852-8. doi: 10.1111/j.1469-0691.2011.03542.x. Epub 2011 Sep 15. — View Citation

Dimopoulos G, Matthaiou DK, Karageorgopoulos DE, Grammatikos AP, Athanassa Z, Falagas ME. Short- versus long-course antibacterial therapy for community-acquired pneumonia : a meta-analysis. Drugs. 2008;68(13):1841-54. doi: 10.2165/00003495-200868130-00004. — View Citation

Dunbar LM, Wunderink RG, Habib MP, Smith LG, Tennenberg AM, Khashab MM, Wiesinger BA, Xiang JX, Zadeikis N, Kahn JB. High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm. Clin Infect Dis. 2003 Sep 15;37(6):752-60. doi: 10.1086/377539. Epub 2003 Aug 28. Erratum In: Clin Infect Dis. 2003 Oct 15;37(8):1147. — View Citation

Egelund GB, Jensen AV, Andersen SB, Petersen PT, Lindhardt BO, von Plessen C, Rohde G, Ravn P. Penicillin treatment for patients with Community-Acquired Pneumonia in Denmark: a retrospective cohort study. BMC Pulm Med. 2017 Apr 20;17(1):66. doi: 10.1186/s12890-017-0404-8. — View Citation

el Moussaoui R, de Borgie CA, van den Broek P, Hustinx WN, Bresser P, van den Berk GE, Poley JW, van den Berg B, Krouwels FH, Bonten MJ, Weenink C, Bossuyt PM, Speelman P, Opmeer BC, Prins JM. Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study. BMJ. 2006 Jun 10;332(7554):1355. doi: 10.1136/bmj.332.7554.1355. — View Citation

File TM Jr, Mandell LA, Tillotson G, Kostov K, Georgiev O. Gemifloxacin once daily for 5 days versus 7 days for the treatment of community-acquired pneumonia: a randomized, multicentre, double-blind study. J Antimicrob Chemother. 2007 Jul;60(1):112-20. doi: 10.1093/jac/dkm119. Epub 2007 May 30. — View Citation

File TM Jr. Clinical efficacy of newer agents in short-duration therapy for community-acquired pneumonia. Clin Infect Dis. 2004 Sep 1;39 Suppl 3:S159-64. doi: 10.1086/421354. — View Citation

Guillemot D, Carbon C, Balkau B, Geslin P, Lecoeur H, Vauzelle-Kervroedan F, Bouvenot G, Eschwege E. Low dosage and long treatment duration of beta-lactam: risk factors for carriage of penicillin-resistant Streptococcus pneumoniae. JAMA. 1998 Feb 4;279(5):365-70. doi: 10.1001/jama.279.5.365. — View Citation

Halm EA, Fine MJ, Marrie TJ, Coley CM, Kapoor WN, Obrosky DS, Singer DE. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. JAMA. 1998 May 13;279(18):1452-7. doi: 10.1001/jama.279.18.1452. — View Citation

Huttner A, Harbarth S, Carlet J, Cosgrove S, Goossens H, Holmes A, Jarlier V, Voss A, Pittet D. Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum. Antimicrob Resist Infect Control. 2013 Nov 18;2:31. doi: 10.1186/2047-2994-2-31. eCollection 2013. — View Citation

Li JZ, Winston LG, Moore DH, Bent S. Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Am J Med. 2007 Sep;120(9):783-90. doi: 10.1016/j.amjmed.2007.04.023. — View Citation

Madaras-Kelly KJ, Burk M, Caplinger C, Bohan JG, Neuhauser MM, Goetz MB, Zhang R, Cunningham FE; Pneumonia Duration of Therapy Medication Utilization Evaluation Group. Total duration of antimicrobial therapy in veterans hospitalized with uncomplicated pneumonia: Results of a national medication utilization evaluation. J Hosp Med. 2016 Dec;11(12):832-839. doi: 10.1002/jhm.2648. Epub 2016 Aug 16. — View Citation

Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2(Suppl 2):S27-72. doi: 10.1086/511159. No abstract available. — View Citation

Menendez R, Torres A, Rodriguez de Castro F, Zalacain R, Aspa J, Martin Villasclaras JJ, Borderias L, Benitez Moya JM, Ruiz-Manzano J, Blanquer J, Perez D, Puzo C, Sanchez-Gascon F, Gallardo J, Alvarez CJ, Molinos L; Neumofail Group. Reaching stability in community-acquired pneumonia: the effects of the severity of disease, treatment, and the characteristics of patients. Clin Infect Dis. 2004 Dec 15;39(12):1783-90. doi: 10.1086/426028. Epub 2004 Nov 18. — View Citation

Pollack LA, Srinivasan A. Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. Clin Infect Dis. 2014 Oct 15;59 Suppl 3(Suppl 3):S97-100. doi: 10.1093/cid/ciu542. — View Citation

Ramirez JA, Wiemken TL, Peyrani P, Arnold FW, Kelley R, Mattingly WA, Nakamatsu R, Pena S, Guinn BE, Furmanek SP, Persaud AK, Raghuram A, Fernandez F, Beavin L, Bosson R, Fernandez-Botran R, Cavallazzi R, Bordon J, Valdivieso C, Schulte J, Carrico RM; University of Louisville Pneumonia Study Group. Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality. Clin Infect Dis. 2017 Nov 13;65(11):1806-1812. doi: 10.1093/cid/cix647. — View Citation

Schrag SJ, Pena C, Fernandez J, Sanchez J, Gomez V, Perez E, Feris JM, Besser RE. Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: a randomized trial. JAMA. 2001 Jul 4;286(1):49-56. doi: 10.1001/jama.286.1.49. — View Citation

Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med. 2017 Sep 1;177(9):1308-1315. doi: 10.1001/jamainternmed.2017.1938. — View Citation

Torres A, Muir JF, Corris P, Kubin R, Duprat-Lomon I, Sagnier PP, Hoffken G. Effectiveness of oral moxifloxacin in standard first-line therapy in community-acquired pneumonia. Eur Respir J. 2003 Jan;21(1):135-43. doi: 10.1183/09031936.03.00045202. — View Citation

Uranga A, Espana PP, Bilbao A, Quintana JM, Arriaga I, Intxausti M, Lobo JL, Tomas L, Camino J, Nunez J, Capelastegui A. Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial. JAMA Intern Med. 2016 Sep 1;176(9):1257-65. doi: 10.1001/jamainternmed.2016.3633. — View Citation

Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012 Jan;67(1):71-9. doi: 10.1136/thx.2009.129502. Epub 2010 Aug 20. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	90-day readmission-free survival		within 90 days
Secondary	Duration of antibiotic treatment	Days that the participant receives antibiotic treatment for pneumonia, adding intravenous and oral therapy	within 90 days
Secondary	Length of hospital stay	Days from the date of hospital admission for pneumonia to the date of discharge	within 90 days
Secondary	Antibiotic adverse events	Number of participants with adverse events with possible relation to the antibiotic treatment of pneumonia	within 90 days
Secondary	Serious adverse events	Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines	within 90 days
Secondary	Major complications	Number of participants with major complications, including pleural effusion, pleural empyema, lung abscess, respiratory failure, severe sepsis, renal failure, use of non-invasive or invasive ventilation, need for vasopressors, and intensive care unit (ICU) admission	within 90 days
Secondary	Use of antimicrobials after discharge	Days of antibiotic treatment for any reason after hospital discharge	within 90 days
Secondary	Post-discharge follow-up visits	Number of participants with medical visits after hospital discharge, including visits at the outpatient clinic and at the general practitioner	within 90 days
Secondary	Readmissions	Number of participants with readmissions for reasons related to or unrelated to pneumonia	days 30 and 90
Secondary	Mortality	Number of deaths by any cause	in-hospital, days 30 and 90