Condition category
Infections and Infestations
Date applied
24/05/2004
Date assigned
11/10/2004
Last edited
15/08/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Najib Rahman

ORCID ID

Contact details

Academic Clinical Lecturer
Oxford Respiratory Trials Unit
University of Oxford
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom

Additional identifiers

EudraCT number

2004-000658-22

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

Multi-centre Intra-pleural Sepsis Trial (MIST2)

Study hypothesis

Pleural infection - an infection of the area around the lungs - can occur when people have lung diseases such as pneumonia. Doctors often try to drain the fluid around the lungs to try to treat this. But sometimes this can be hard to do successfully. Some people have to have an operation, and some people may die as a result of the infection. Researchers think that the drugs DNase and Alteplase, which are already used to treat other illnesses, might help to treat pleural infection. The MIST2 trial aims to test whether these drugs are safe, and whether they can help to drain the fluid around the lungs. We are doing this trial in partnership with the Respiratory Trials Unit at the Churchill Hospital, Oxford.

Ethics approval

Eastern Multi-Research Ethics Committee (latterly Cambridgeshire 4 REC) on 16/12/2004
(ref: 04/mre05/53)

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Pleural infection

Intervention

Patients will be randomly assigned in the ratio 1:1:1:1 to either of the following regimes:
Alteplase 10 mg bd (twice a day) intrapleurally + DNase 5 mg bd intrapleurallly; or
Alteplase placebo intrapleurally + DNase 5 mg bd intrapleurally; or
Alteplase 10 mg bd intrapleurally + DNase placebo intrapleurally; or
Alteplase placebo intrapleurally + DNase placebo intrapleurally.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

The primary endpoint will be radiographic improvement in area of pleural collection (between the area of the pleural collection on the CXR at randomisation and the chest radiograph taken on day 6/7).

Secondary outcome measures

Secondary outcome measure(s):
1. Changes in blood CRP from baseline to day 6/7
2. Time from randomisation to remain apyrexial for 36 hrs
3. Total pleural fluid drainage
4. Survival and need for surgery at 3 and 12 months

Overall trial start date

11/10/2003

Overall trial end date

11/10/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1.A clinical presentation compatible with pleural infection
2. Has pleural fluid requiring drainage which is either purulent, gram stain positive, culture positive or acidic with a pH<7.2
3. Written informed consent

Participant type

Patient

Age group

Not Specified

Gender

Both

Target number of participants

Added as of 10/09/2007: 210

Participant exclusion criteria

1. Age <18 years
2. Has previously received intra-pleural fibrinolytics or DNase for this empyema
3. Has a known sensitivity to DNase or tissue plasminogen activator
4. Has had a coincidental stroke, a major haemorrhage or major trauma
5. Has had major surgery in the previous 5 days
6. Has had a previous pneumonectomy on the side of infection
Patients who are pregnant or lactating (females of childbearing potential must have a negative pregnancy test before randomisation)
Expected survival less than three months from a different pathology to this empyema (e.g. metastatic lung carcinoma)
Inability to give informed consent

Recruitment start date

11/10/2003

Recruitment end date

11/10/2007

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Academic Clinical Lecturer
Oxford
OX3 7LJ
United Kingdom

Sponsor information

Organisation

Oxford Radcliffe Hospitals NHS Trust (UK)

Sponsor details

R&D Office
Manor House
The John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Sponsor type

Government

Website

Funders

Funder type

Industry

Funder name

Unrestricted educational grant from Roche 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

1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21830966

Publication citations

  1. Results

    Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ, Intrapleural use of tissue plasminogen activator and DNase in pleural infection., N. Engl. J. Med., 2011, 365, 6, 518-526, doi: 10.1056/NEJMoa1012740.

Additional files

Editorial Notes