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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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
Inschrijving (Werkelijk)
Fase
- Niet toepasbaar
Contacten en locaties
Studie Locaties
-
-
-
Alexandria, Egypte
- ALEXANDRIA UNIVERSITY FACULTY OF MEDICINE
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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).
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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
|
|
Actieve vergelijker: Long course
Antibiotic course of 4-6 weeks overall duration for treating pleural infection
|
4-6 weeks of antibiotics
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Number of participants with failure of medical treatment
Tijdsspanne: 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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Length of antibiotic treatment in days
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 30 days from discharge
|
Readmission within 30 days from discharge
|
30 days from discharge
|
Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Hoofdonderzoeker: Maged Hassan, PhD, ALEXANDRIA UNIVERSITY FACULTY OF MEDICINE
Publicaties en nuttige links
Algemene publicaties
- 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.
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 3/24/11/10/2020
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
IPD-tijdsbestek voor delen
IPD-toegangscriteria voor delen
IPD delen Ondersteunend informatietype
- LEERPROTOCOOL
- SAP
- ICF
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .