Condition category
Respiratory
Date applied
07/03/2007
Date assigned
30/04/2007
Last edited
19/05/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Mrs Emma Hedley

ORCID ID

Contact details

Respiratory Trials Unit
Oxford Centre for Respiratory Medicine
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom

Additional identifiers

EudraCT number

2006-006630-18

ClinicalTrials.gov number

Protocol/serial number

TIME 2

Study information

Scientific title

Acronym

The second therapeutic intervention in malignant effusion trial (TIME2)

Study hypothesis

A cancer induced collection of fluid between the lung and the chest wall (a pleural effusion) affects about 250,000 new patients each year (UK&US), including 25% of patients with lung cancer, 95% with mesothelioma and 40% with breast cancer. The accumulated fluid compresses the lung causing disabling breathlessness that requires painful pleural procedures to drain the fluid. Standard care includes adhering the lung to the chest wall (pleurodesis) which is painful and must be repeated in about 20% of patients. This is then followed by repeated fluid drainage if it fails. These procedures carry significant costs.
The advent of ‘tunnelled’ ambulatory small-bore chest catheters, drained as required by patients and their carers, presents a different and potentially better strategy. Treatment could be almost entirely outpatient, with the patient controlling their drainage and free from the pain and costs of pleurodesis/drainage; though with the disadvantage of the indwelling catheter. Patients able to promptly drain their own catheter as needed should produce better breathlessness control than intermittent hospital treatment (the primary aim of pleurodesis). This study is a randomised trial which will compare how well breathlessness is controlled by an indwelling catheter compared to standard care in 114 patients with cancer induced pleural effusion and will measure the frequency of problems with the two treatment strategies. If this trial is positive, it will directly improve care for one of the commonest respiratory problems, to the benefit of >250,000 patients each year.

Ethics approval

Milton Keynes Local Research Ethics Committee (ref: 07/Q1603/2)

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 effusion

Intervention

Patients will be randomly assigned (1:1) to either an indwelling ambulatory pleural catheter or standard care for their malignant pleural effusion.
Computer derived allocation will be delivered by the established Oxford/London MRC Clinical Trials Unit systems. In order to minimise biases in trial results randomisation will include minimisation for histological tissue type (mesothelioma vs. non-mesothelioma) as survival is increased in mesothelioma, and the risk of catheter associated subcutaneous tumour invasion may be higher with mesothelioma, and for WHO performance status (0/1 vs. 2/3).

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

The primary outcome will be the average daily Visual Analogue Scale (VAS) defining breathlessness, after removing "breathlessness unresponsive to pleural fluid drainage" - defined as the VAS following first complete pleural fluid drainage. Patients will also record how much their breathlessness has bothered them each day. The daily VAS will be performed at a similar time each day. The patients will perform VAS and record breathlessness for 6 weeks.

Secondary outcome measures

The following will be assessed at time of the primary outcome measure and recorded throughout the year of the trial:
1. Average daily chest pain assessed using VAS score for 6 weeks
2. Self reported health status (‘quality of life’) assessed using Chronic Respiratory Disease Questionnaire (CRDQ) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30)
3. Economic assessment: direct quantification of clinical costs from patient kept diary records and estimated health care costs (Euroqol-5 Dimensions [EQ-5D] Questionnaire)
4. Spontaneous pleurodesis rate with ambulatory catheters (This will differ for each patient and will be recorded individually)
5. Complication rate with ambulatory catheters (Any complications that arise will be documented throughout the duration of the study)

Overall trial start date

01/04/2006

Overall trial end date

01/01/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Clinically confident diagnosis of malignant pleural effusion requiring pleurodesis. The diagnosis may be established by:
a. Histocytologically proven pleural malignancy or
b. Recurrent large pleural effusion in the context of histologically proven cancer outside the thorax.
2. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

114

Participant exclusion criteria

1. Age < 18 years
2. Beginning chemotherapy in the next 4 weeks
3. Expected survival <3 months
4. Chylothorax
5. Previous lobectomy or pneumonectomy on the side of the effusion
6. Previous attempted pleurodesis
7. Pleural infection
8. Total blood white cell count <1.0 x 109
9. Hypercapnic ventilatory failure
10. Patients who are pregnant or lactating
11. Irreversible bleeding diathesis
12. Irreversible visual impairment
13. Inability to give informed consent or comply with the protocol

Recruitment start date

01/04/2006

Recruitment end date

01/01/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Respiratory Trials Unit
Oxford
OX3 7LJ
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trials and Research Governance
Manor House
The John Radcliffe Hospital
Headington
Oxford
OX3 9DZ
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

British Lung Foundation (UK)

Alternative name(s)

BLF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

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

2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22610520
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24832000

Publication citations

  1. Results

    Davies HE, Mishra EK, Kahan BC, Wrightson JM, Stanton AE, Guhan A, Davies CW, Grayez J, Harrison R, Prasad A, Crosthwaite N, Lee YC, Davies RJ, Miller RF, Rahman NM, Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial., JAMA, 2012, 307, 22, 2383-2389, doi: 10.1001/jama.2012.5535.

  2. Results

    Penz ED, Mishra EK, Davies HE, Manns BJ, Miller RF, Rahman NM, Comparing Cost of Indwelling Pleural Catheter vs. Talc Pleurodesis for Malignant Pleural Effusion., Chest, 2014, doi: 10.1378/chest.13-2481.

Additional files

Editorial Notes