Short Versus Long Antibiotic Course for Pleural Infection Management (SLIM Trial)

NCT04615286 | Completed

• 1 other identifier: 3/24/11/10/2020
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pleural Infection

Outcome Measures

Primary Outcomes (1)

• Number of participants with failure of medical treatment

  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

Secondary Outcomes (4)

• Length of antibiotic treatment in days

  Outcome assessed at six weeks post diagnosis

• Number of participants with chest X ray worsening at 6 weeks

  Outcome assessed at six weeks post diagnosis

• Time to return to normal daily activities in days

  Outcome assessed at six weeks post diagnosis

• Number of participants requiring readmission within 30 days from discharge

  30 days from discharge

Study Arms (2)

Short course

EXPERIMENTAL

Antibiotic course of 2-3 weeks overall duration for treating pleural infection

Other: Short course (2-3 weeks) of antibiotics

Long course

ACTIVE COMPARATOR

Antibiotic course of 4-6 weeks overall duration for treating pleural infection

Other: Standard (long course) of antibiotics

Interventions

Short course (2-3 weeks) of antibiotics OTHER

Shorter course of antibiotic than standard care of 4-6 weeks

Short course

Standard (long course) of antibiotics OTHER

4-6 weeks of antibiotics

Long course

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Alexandria University: lead

Study Sites (1)

Alexandria University Faculty of Medicine

Alexandria, Egypt

Location

Related Publications (9)

• 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.

  PMID: 20696693 BACKGROUND

• 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.

  PMID: 31391221 BACKGROUND

• 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.

  PMID: 15142871 BACKGROUND

• 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.

  PMID: 32675200 BACKGROUND

• 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.

  PMID: 30005142 BACKGROUND

• 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.

  PMID: 31248959 BACKGROUND

• 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.

  PMID: 26350935 BACKGROUND

• 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.

  PMID: 26022948 BACKGROUND

• 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.

  PMID: 24264558 BACKGROUND

MeSH Terms

Interventions

Anti-Bacterial Agents

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Maged Hassan, PhD

  Alexandria University Faculty of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2020
• First Posted: November 4, 2020
• Study Start: September 28, 2020
• Primary Completion: November 10, 2021
• Study Completion: December 6, 2021
• Last Updated: December 21, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 5 years after study completion
• Access Criteria: The data that support the findings of this study will be available on request from the corresponding author upon publishing the manuscript with the main results.

Locations

EG (1)