Shortened Antibiotic Treatment of 5 Days in Community-Acquired Pneumonia

NCT04089787 | Completed Phase 4 DMC

• 2 other identifiers: H-190144792019-000404-15
• Study Type: interventional
• Target: 395
• Locations: 1 country
• Sites: 7

Brief 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. Three to 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 survival which will be tested with a non-inferiority margin of 6%.

Conditions

Community-acquired Pneumonia

Keywords

Community-acquired pneumonia; Treatment duration; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Bacterial Infections; Pneumonia, Bacterial; Anti-Infective Agents; Anti-Bacterial Agents

Outcome Measures

Primary Outcomes (1)

• 90-day survival

  within 90 days

Secondary Outcomes (9)

• Duration of antibiotic treatment

  within 90 days

• Length of hospital stay

  within 90 days

• Antibiotic adverse events

  within 90 days

• Serious adverse events

  within 90 days

• Major complications

  within 90 days

Study Arms (2)

Intervention group

EXPERIMENTAL

Shortened antibiotic treatment of 5 days

Other: Intervention

Control group

ACTIVE COMPARATOR

Antibiotic treatment of 7 days or longer at the discretion of the treating physician

Other: Control

Interventions

Intervention OTHER

Shortened antibiotic treatment of 5 days

Intervention group

Control OTHER

Antibiotic treatment of 7 days or longer at the discretion of the treating physician

Control group

Eligibility Criteria

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

You may qualify if:

• Hospitalized with community-acquired pneumonia; defined as new pulmonary infiltrate on chest X-ray and/or CT scan 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%)

You may not qualify if:

• 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, directed at lower respiratory tract pathogens
• 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

Sponsors & Collaborators

• Thomas Benfield: lead

Study Sites (7)

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Bispebjerg Hospital

Copenhagen, 2400, Denmark

Location

Gentofte Hospital

Gentofte Municipality, 2900, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Nordsjællands Hospital

Hillerød, 3400, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

Related Publications (25)

• 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.

  PMID: 20729232 BACKGROUND

• 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.

  PMID: 29020164 BACKGROUND

• 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.

  PMID: 28427381 BACKGROUND

• 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.

  PMID: 27455166 BACKGROUND

• 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.

  PMID: 28666965 BACKGROUND

• 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.

  PMID: 12955634 BACKGROUND

• 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.

  PMID: 16763247 BACKGROUND

• 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.

  PMID: 12570122 BACKGROUND

• 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.

  PMID: 17537866 BACKGROUND

• 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.

  PMID: 28604925 BACKGROUND

• 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.

  PMID: 24237856 BACKGROUND

• 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.

  PMID: 25261548 BACKGROUND

• 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.

  PMID: 27527659 BACKGROUND

• 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.

  PMID: 19926738 BACKGROUND

• 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.

  PMID: 17765048 BACKGROUND

• 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.

  PMID: 18729535 BACKGROUND

• 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.

  PMID: 17278083 BACKGROUND

• 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.

  PMID: 11434826 BACKGROUND

• 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.

  PMID: 14625336 BACKGROUND

• 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.

  PMID: 15546111 BACKGROUND

• 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.

  PMID: 9459469 BACKGROUND

• 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.

  PMID: 9600479 BACKGROUND

• 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.

  PMID: 15578400 BACKGROUND

• 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.

  PMID: 21919994 BACKGROUND

• Israelsen SB, Tingsgard S, Thorlacius-Ussing L, Knudsen A, Lindegaard B, Johansen IS, Mygind LH, Ravn P, Benfield T. Short-course antibiotic therapy of 5 days in community-acquired pneumonia (CAP5): study protocol for a randomised controlled trial. BMJ Open. 2023 Jul 21;13(7):e069013. doi: 10.1136/bmjopen-2022-069013.

  PMID: 37479519 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Bacterial Infections; Pneumonia, Bacterial

Interventions

Methods

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• Simone Bastrup Israelsen, MD

  Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: September 13, 2019
• Study Start: September 18, 2019
• Primary Completion: January 22, 2025
• Study Completion: January 22, 2025
• Last Updated: April 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (7)