Short Versus Long Antibiotic Course for Pleural Infection Management (SLIM Trial) (SLIM)
Short Versus Long Antibiotic Course for Pleural Infection Management (SLIM Trial): a Randomized Controlled Open Label Trial
Infection of the pleural space is serious condition that requires hospitalization, invasive interventions and long courses of antibiotics[1]. Treatment of pleural infection requires long hospital admission with a median of 19 days[2] and medical treatments fails requiring surgical intervention in up to 30% of cases[3]. The mortality from pleural infection is around 10% at 3 months[4].
Besides drainage of the infected fluid, antibiotics are a core component of management of pleural infection[5] and are typically given intravenously in the first few days of treatment until the condition is stabilized at which stage patients are shifted to oral antibiotics of equivalent spectrum. In almost half of the cases of pleural infection, the choice of antibiotics is entirely empirical due to low yield of microbiological tests on pleural fluid in these cases[6]. International guidelines cite a minimum length of antibiotic course of pleural infection of four weeks[5,7] with antibiotic courses typically lasting six weeks[8]. However, these recommendations are based on expert opinion with no robust evidence to support such durations.
The RAPID (renal function, age, purulence, infection source and dietary factors) score has recently been validated as a robust tool to predict 3-month mortality of patients with pleural infection based on demographic and laboratory data (table 1)[4]. A low score (0-2) is associated with 2-3% mortality, medium score (3-4) 9% mortality and high score (5-7) 30% mortality at three months[9]. The utility for this score in clinical management is yet to be determined and this study will attempt using this score to stratify lengths of antibiotic treatment based on proposed risk of adverse outcomes as stipulated by the RAPID score.
The aim of this study is to investigate the feasibility and safety of prescribing shorter courses of antibiotics (2-3 weeks) versus the standard longer courses (4-6 weeks) in medically-treated patients with pleural infection at lower risk of mortality (RAPID score 0-4) who can be safely discharged home within 14 days of hospitalization and how this impacts success of medical treatment.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Infection of the pleural space is serious condition that requires hospitalization, invasive interventions and long courses of antibiotics. Treatment of pleural infection requires long hospital admission with a median of 19 days and medical treatments fails requiring surgical intervention in up to 30% of cases. The mortality from pleural infection is around 10% at 3 months.
Besides drainage of the infected fluid, antibiotics are a core component of management of pleural infection and are typically given intravenously in the first few days of treatment until the condition is stabilized at which stage patients are shifted to oral antibiotics of equivalent spectrum. In almost half of the cases of pleural infection, the choice of antibiotics is entirely empirical due to low yield of microbiological tests on pleural fluid in these cases. International guidelines cite a minimum length of antibiotic course of pleural infection of four weeks with antibiotic courses typically lasting six weeks[8]. However, these recommendations are based on expert opinion with no robust evidence to support such durations. A recent trial compared a two-week versus a three-week antibiotic course for parapneumonic pleural infections. The trial that concluded prematurely due to inability to recruit to target sample size and found that the two regimens were equivalent in terms of risk of failure of medical treatment. Besides being an underpowered study, the results are only applicable to parapneumonic effusions but not primary pleural infections.
The RAPID score has recently been validated as a robust tool to predict 3-month mortality of patients with pleural infection based on demographic and laboratory data. A low score (0-2) is associated with 2-3% mortality, medium score (3-4) 9% mortality and high score (5-7) 30% mortality at three months. The utility for this score in clinical management is yet to be determined and this study will attempt using this score to stratify lengths of antibiotic treatment based on proposed risk of adverse outcomes as stipulated by the RAPID score. A shorter antibiotic course that is as effective as the standard long course is desirable given the common occurrence of side effects with antibiotic treatment. The presence of a robust predictive score of outcome seems as an attractive tool to help stratify patients who can be safely treated with shorter antibiotic courses.
The aim of this study is to investigate the feasibility and safety of prescribing shorter courses of antibiotics (2-3 weeks) versus the standard longer courses (4-6 weeks) in medically-treated patients with pleural infection at lower risk of mortality (RAPID score 0-4) who can be safely discharged home within 14 days of hospitalization and how this impacts success of medical treatment.
Studietype
Registrering (Faktiske)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiesteder
-
-
-
Alexandria, Egypt
- ALEXANDRIA UNIVERSITY FACULTY OF MEDICINE
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- Adult patients (>18 years old)
- Willing to provide informed consent
Admitted to hospital for treatment of pleural infection (both parapneumonic and primary pleural infections included). Pleural infection will be defined by the presence of one of the following:
- the presence of pus in the pleural space;
- positive pleural fluid gram stain or culture; or
- pleural fluid pH < 7.2 or pleural fluid glucose < 40 mg/dL in the setting of acute respiratory infection.
- RAPID low or intermediate score (0-4)
- Fit for discharge within 14th day of admission
Exclusion Criteria:
- Failure of medical treatment within 14 days of admission and need for surgical referral
- Need for hospital admission beyond 14 days due to medical reasons
- Admission to recurrent ipsilateral pleural infection within the last three months
- RAPID high score (5 or more)
- Pleural infection not amenable to drainage at time of diagnosis and therefore upfront decision to treat with prolonged antibiotics
- Residual pleural collection (despite attempted drainage) that the managing clinician indicated is for prolonged oral suppressive therapy (i.e. six weeks of oral antibiotics).
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Short course
Antibiotic course of 2-3 weeks overall duration for treating pleural infection
|
Shorter course of antibiotic than standard care of 4-6 weeks
|
|
Aktiv komparator: Long course
Antibiotic course of 4-6 weeks overall duration for treating pleural infection
|
4-6 weeks of antibiotics
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of participants with failure of medical treatment
Tidsramme: Outcome assessed at six weeks post diagnosis
|
Incidence of failure of treatment as judged by trial clinician requiring further antibiotics and/or tube drainage and/or surgical intervention by six weeks post initial admission.
Failure will be determined based on the one or more of the following parameter: clinical (recurrence of symptoms), biochemical (worsening of WCC [by 2000/mm3] or CRP [by > 20%] from discharge values) and radiological (chest X-ray +/- TUS evidence of increasing or new pleural collection).
|
Outcome assessed at six weeks post diagnosis
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Length of antibiotic treatment in days
Tidsramme: Outcome assessed at six weeks post diagnosis
|
Total length of antibiotic treatment (in days) in the study arms
|
Outcome assessed at six weeks post diagnosis
|
|
Number of participants with chest X ray worsening at 6 weeks
Tidsramme: Outcome assessed at six weeks post diagnosis
|
Number of participants with worsening in the 6-week chest X-ray as compared to discharge chest X-ray in the study arms.
Chest X-ray pairs (discharge vs 6-week) will be read by a respiratory physician blinded to treatment allocation who will judge whether there is worsening (versus stability or improvement)
|
Outcome assessed at six weeks post diagnosis
|
|
Time to return to normal daily activities in days
Tidsramme: Outcome assessed at six weeks post diagnosis
|
Time (in days) to return to normal daily activities in participants of the study arms
|
Outcome assessed at six weeks post diagnosis
|
|
Number of participants requiring readmission within 30 days from discharge
Tidsramme: 30 days from discharge
|
Readmission within 30 days from discharge
|
30 days from discharge
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Maged Hassan, PhD, ALEXANDRIA UNIVERSITY FACULTY OF MEDICINE
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Davies HE, Davies RJ, Davies CW; BTS Pleural Disease Guideline Group. Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010 Aug;65 Suppl 2:ii41-53. doi: 10.1136/thx.2010.137000. No abstract available.
- Hooper CE, Edey AJ, Wallis A, Clive AO, Morley A, White P, Medford AR, Harvey JE, Darby M, Zahan-Evans N, Maskell NA. Pleural irrigation trial (PIT): a randomised controlled trial of pleural irrigation with normal saline versus standard care in patients with pleural infection. Eur Respir J. 2015 Aug;46(2):456-63. doi: 10.1183/09031936.00147214. Epub 2015 May 28.
- Rahman NM, Kahan BC, Miller RF, Gleeson FV, Nunn AJ, Maskell NA. A clinical score (RAPID) to identify those at risk for poor outcome at presentation in patients with pleural infection. Chest. 2014 Apr;145(4):848-855. doi: 10.1378/chest.13-1558.
- Cargill TN, Hassan M, Corcoran JP, Harriss E, Asciak R, Mercer RM, McCracken DJ, Bedawi EO, Rahman NM. A systematic review of comorbidities and outcomes of adult patients with pleural infection. Eur Respir J. 2019 Oct 1;54(3):1900541. doi: 10.1183/13993003.00541-2019. Print 2019 Sep.
- Corcoran JP, Psallidas I, Gerry S, Piccolo F, Koegelenberg CF, Saba T, Daneshvar C, Fairbairn I, Heinink R, West A, Stanton AE, Holme J, Kastelik JA, Steer H, Downer NJ, Haris M, Baker EH, Everett CF, Pepperell J, Bewick T, Yarmus L, Maldonado F, Khan B, Hart-Thomas A, Hands G, Warwick G, De Fonseka D, Hassan M, Munavvar M, Guhan A, Shahidi M, Pogson Z, Dowson L, Popowicz ND, Saba J, Ward NR, Hallifax RJ, Dobson M, Shaw R, Hedley EL, Sabia A, Robinson B, Collins GS, Davies HE, Yu LM, Miller RF, Maskell NA, Rahman NM. Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study. Eur Respir J. 2020 Nov 26;56(5):2000130. doi: 10.1183/13993003.00130-2020. Print 2020 Nov. Erratum In: Eur Respir J. 2020 Dec 17;56(6):
- Maskell NA, Lee YC, Gleeson FV, Hedley EL, Pengelly G, Davies RJ. Randomized trials describing lung inflammation after pleurodesis with talc of varying particle size. Am J Respir Crit Care Med. 2004 Aug 15;170(4):377-82. doi: 10.1164/rccm.200311-1579OC. Epub 2004 May 13.
- Bedawi EO, Hassan M, Rahman NM. Recent developments in the management of pleural infection: A comprehensive review. Clin Respir J. 2018 Aug;12(8):2309-2320. doi: 10.1111/crj.12941.
- Hassan M, Cargill T, Harriss E, Asciak R, Mercer RM, Bedawi EO, McCracken DJ, Psallidas I, Corcoran JP, Rahman NM. The microbiology of pleural infection in adults: a systematic review. Eur Respir J. 2019 Oct 1;54(3):1900542. doi: 10.1183/13993003.00542-2019. Print 2019 Sep.
- Bhatnagar R, Maskell N. The modern diagnosis and management of pleural effusions. BMJ. 2015 Sep 8;351:h4520. doi: 10.1136/bmj.h4520. No abstract available.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 3/24/11/10/2020
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
IPD-delingstidsramme
Tilgangskriterier for IPD-deling
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
- ICF
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .