Condition category
Respiratory
Date applied
16/05/2012
Date assigned
22/05/2012
Last edited
20/05/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Pleural infection (infection between the two linings of the lung) is a common and serious medical condition. It frequently follows pneumonia although rarely occurs as a primary disease. While pleural infection can occur at any age, within the adult population, it is most common in the elderly and in patients with other diseases such as diabetes. Up to 15% of patients with pleural infection do not survive the episode.
Currently, the best available primary treatment is a combination of antibiotics (given into a vein, usually for at least 7 days) and drainage of fluid/pus from the pleural space via a tube that remains in place for some days (a chest drain). This treatment is not fully effective for a significant proportion of patients, resulting in worsening or ongoing grumbling infection or persistent breathlessness after the initial illness due to residual scarring and thickening of the lining of the lung. In these cases (up to 40%) patients require a surgical procedure. ‘Decortication’ procedures are performed by cardiothoracic surgeons under general anaesthetic with the aim of clearing all infected and abnormal tissue from the lining of the lung. The best timing and patient factors that indicate the need for surgery are not known and practice amongst respiratory physicians varies. Surgical procedures are associated with a risk of serious complications and many patients with pleural infection are unfit for a general anaesthetic, leaving them with limited options.
The most common cause of failure of simple treatment with antibiotics and a chest tube (resulting in the need for a surgical procedure) is inadequate drainage of thick pleural fluid (fluid in between the linings of the lung). This issue has been the subject of significant research which has told us that larger tubes and drugs (fibrinolytics) that break down pockets within the fluid do not improve drainage.
There may be a simpler solution. European centres are increasingly using saline irrigation into chest drains in the primary treatment of pleural infection. Although success rates are impressive, avoiding the need to operate on most patients, there have been no published trials to allow it to be extended into global clinical practice. Irrigation has been used after operations in patients with pleural infection and published results suggests that it may reduce the need for second surgical procedures.
Irrigation is a simple and inexpensive treatment that has not been associated with serious side effects. It employs 0.9% saline (commonly used as a physiological solution to rehydrate patients and to clean and irrigate wounds) which is infused into the chest cavity via the chest drain every six hours to effectively wash out the pleural space and thin pleural fluid so it drains more easily.

Who can participate?
This study will recruit 40 patients with pleural infection.

What does the study involve?
Participants will be randomly allocated to receive either saline irrigation through their chest drain or standard chest drain management with small volume saline flushes. Each patient will receive nine doses of either irrigation or flushes over a three-day period. Patients will undergo a CT and ultrasound scan at the beginning and the end of the trial to look for any improvement. Blood tests (including measurement of a blood protein, procalcitonin, which may be a marker of severity of the infection), patient experience and need for surgery for pleural infection will also be monitored. Patients will be followed up for 4 months after trial entry.

What are the possible benefits and risks of participating?
If the patient is allocated to saline irrigation, it is possible that they will benefit from this promising treatment. Whichever group a patient is allocated to, they will be contributing to our understanding and development of new, better ways to treat pleural infection which will benefit patients in the future. The pilot study data will allow the development of a multicentre trial. Positive results would change clinical practice, potentially leading to reduced death rates, especially in those not fit enough for surgery. There are no specific risks associated with saline irrigation but trial involvement does involve one extra CT scan, which is associated with exposure to additional radiation equivalent to about 4-5 years of background radiation.

Where is the study run from?
North Bristol NHS Trust (UK).

When is the study starting and how long is it expected to run for?
The study opened to recruitment in November 2009 and will close in July 2012.

Who is funding the study?
The study is funded by a small grants award from North Bristol NHS Trust and the company, Biomerieux, who supplied the equipment to measure procalcitonin levels.

Who is the main contact?
Dr Nick Maskell
nick.maskell@bristol.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Nick Maskell

ORCID ID

Contact details

North Bristol NHS Trust
Southmead Hospital
Bristol
BS10 5NB
United Kingdom
-
nick.maskell@bristol.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NBT Rand D number: 2224

Study information

Scientific title

A randomised controlled pilot study comparing intrapleural saline irrigation with simple tube drainage in the management of pleural infection

Acronym

PIT-1

Study hypothesis

1. Is saline irrigation superior to standard care in the management of pleural infection as measured by early radiological and clinical improvement?
2. Is saline irrigation superior to standard care in the management of pleural infection as measured by reduction in the need for surgical referral?
3. Are serum and pleural fluid procalcitonin levels useful in monitoring the progress of patients with pleural infection and can they predict outcome?
4. Is procalcitonin a superior marker to serum C reactive protein (CRP) in this setting?
5. Does the microbiology of throat swabs taken at presentation predict bacterial growth from pleural fluid?

Ethics approval

Southmead Hospital Research Ethics Committee, October 2009, ref: 09/H0102/58

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Pleural infection

Intervention

Patients will undergo blood tests at baseline and daily during the trial. They will receive antibiotics for pleural infection as per hospital guidelines and will have a 12-14Fr chest tube inserted as treatment for infection. This will be flushed 3 times per day with 20ml 0.9% saline and meticulous records will be kept of drainage volumes. Pleural fluid will be sent for culture.

12-72 hours following drain placement patients will undergo a CT thorax with pleural contrast (Trial scan). Patients with no fluid or thickening present on CT will be excluded from randomisation at this stage and the chest drain removed (standard care). They will also have a bedside ultrasound performed.

Patients will be randomised to saline irrigation or standard care with minimisation for volume of pleural fluid on CT scan (< 25% hemithorax or < 25% hemithorax occupied by pleural fluid), and presence or absence of septation/loculation on bedside pleural ultrasound. Day 1 begins at randomisation.

Saline irrigation group
250ml 0.9% saline will be administered to the pleural space via the patients chest drain 3 times per day for 3 days (9 doses). Patients will complete a visual analogue scale (VAS) comfort score following 2 irrigations.

Standard care group
20 ml 0.9% saline flushes administered via the patients chest drain 3 times per day for 3 days (9 doses). Patients will complete a VAS comfort score following 2 flushes.

Daily monitoring day 1-6
Observations: Temperature and blood pressure.
Blood tests: Full blood count (FBC), albumin, C-reactive protein (CRP), procalcitonin level.
Chest x-ray alternate days.

After nine irrigations or flushes
Pleural phase contrast CT thorax scan done on day 4-6 (standard care). Clinical decision whether to refer for surgical intervention. If not referred, chest tube removed and discharged with 14 days oral antibiotics as per NBLC protocol (standard care).

Clinic follow-up at 4 and 12 weeks post discharge (standard care), which will include a chest x-ray, FBC, CRP, serum albumin.
Simple spirometry at 12 weeks (standard care).
Serum procalcitonin at 4 and 12 weeks (trial test).

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

Change in volume of pleural fluid between 12 - 72 hours and 4-9 days post chest drain placement (before and after 9 irrigations/flushes) as assessed on CT scan with volumetric reporting.

Secondary outcome measures

1. Change in volume of pleural thickening between 12-72 hours and 4-9 days post chest drain placement as assessed on CT with volumetric reporting
2. Percentage of patients requiring surgery at 4 and 12 weeks post trial entry
3. Percentage of patients referred for surgery at 6 days post chest drain placement
4. Length of in-patient hospital stay
5. Mortality at 12 weeks
6. Change in volume of pleural thickening between 12-72 hours and 12 weeks post drain placement as assessed by chest x-ray
7. Change in volume of pleural fluid and thickening between baseline and completion of 9 irrigations/ flushes on chest x-ray
8. Change in loculation score on ultrasound (see annex 4) between 12-24 hours post drain placement and completion of 9 irrigations
9. Time for CRP to fall to 50% of day 0 value
10. Time for CRP to fall to less than 100 mg/l
11. Serial serum and pleural fluid procalcitonin levels with correlation to surgical referral rates and CRP
12. Spirometry (Forced vital capacity) as percentage predicted at 12 weeks (patients with previously diagnosed respiratory disease excluded from this analysis)

Overall trial start date

23/11/2009

Overall trial end date

16/07/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Clinical presentation consistent with pleural infection requiring chest tube drainage
2. Pleural fluid is:
2.1. Purulent
2.2. Gram stain or culture positive
2.3. pH >7.2

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Participant exclusion criteria

1. Inability to give informed written consent
2. Pregnancy or lactation
3. Age < 18 years
4. Previous thoracic surgery for pleural infection
5. Drain size > 14F already placed or drain placed >72 hours ago

Recruitment start date

23/11/2009

Recruitment end date

16/07/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

North Bristol NHS Trust
Bristol
BS10 5NB
United Kingdom

Sponsor information

Organisation

North Bristol NHS Trust (UK)

Sponsor details

Southmead Hospital
Bristol
BS10 5NB
United Kingdom
-
helen.lewis@nbt.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.nbt.nhs.uk/

Funders

Funder type

Government

Funder name

North Bristol Small Grant Scheme (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Biomerieux Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26022948

Publication citations

Additional files

Editorial Notes

20/05/2016: Publication reference added.