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
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
-
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.
-
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.