The first Therapeutic Interventions in Malignant Effusion trial

ISRCTN	ISRCTN33288337
DOI	https://doi.org/10.1186/ISRCTN33288337
EudraCT/CTIS number	2005-005226-31
ClinicalTrials.gov number	NCT00644319
Secondary identifying numbers	1.1

Submission date: 11/03/2006
Registration date: 19/04/2006
Last edited: 31/03/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-to-find-the-best-way-of-controlling-pain-during-and-after-pleurodesis

Contact information

Dr Robert Davies
Scientific

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

Study information

Study design	2 x 2 randomised factorial trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	The first Therapeutic Interventions in Malignant Effusion trial
Study acronym	TIME1
Study objectives	The TIME1 study is a 2 x 2 randomised factorial trial to assess whether non-steroidal (ibuprofen) analgesia and the use of small bore chest tubes will reduce pain during pleurodesis for malignant effusion, compared to standard care. The trial will also define whether non-steroidal use decreases pleurodesis efficacy.
Ethics approval(s)	West Essex Local Research Ethics Committee, 24/04/2006, ref: 05/Q0301/61
Health condition(s) or problem(s) studied	Malignant pleural effusion, including mesothelioma
Intervention	Participants will undergo normal care (thoracoscopy and talc poudrage or talc slurry pleurodesis via drain), using standardised pre-procedure sedation and analgesia as per protocol. The sizes of chest tubes to be used are predefined (large [24F] and small [12F]). The analgesic regimens are: 1. NSAID: ibuprofen 800 mg three times daily (tds) to a maximum of 8-hourly 2. Opiate: diamorphine 2.5 mg, intravenous (IV) administration, four times daily (qds) to a maximum of 10 mg 3. Rescue: patients will always have access to rescue analgesia as required (diamorphine 2.5 mg IV) Treatment continues from pleurodesis (day 0) to tube removal (day 3). Participants will be randomised to one of the following arms: 1. Large bore (24F) chest drain and NSAID-based analgesic regimen 2. Small bore (12F) chest drain and NSAID-based analgesic regimen 3. Large bore chest drain (24F) and opiate-based analgesic regimen 4. Small bore chest drain (12F) and opiate-based analgesic regimen
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Ibuprofen
Primary outcome measure	Pain score over 72 hours post pleurodesis for malignant pleural effusion, taken by administering 100 mm visual analogue pain score (VAS), to calculate the total pain relief (TOTPAR) score, over 3 days
Secondary outcome measures	1. Success of pleurodesis at six weeks and three months post randomisation (time to relapse of pleural effusion, survival analysis) 2. Presence of chronic chest pain on the side of the pleurodesis at six weeks and three months post randomisation
Overall study start date	26/03/2007
Completion date	31/12/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	320 (interim analysis after 120 patients)
Total final enrolment	320
Key inclusion criteria	1. Clinically confident diagnosis of malignant pleural effusion requiring pleurodesis Definitions: 1.1. Histologically proven pleural malignancy 1.2. Typical features of pleural malignancy seen on direct vision during thoracoscopy 1.3. Pleural effusion in the context of histologically proven cancer elsewhere 2. Written informed consent 3. Expected survival more than one month
Key exclusion criteria	1. Age less than 18 years 2. Primary lymphoma or small cell lung carcinoma 3. Patients who are pregnant or lactating 4. Inability to give informed consent 5. History of gastrointestinal (GI) bleeding or of untreated peptic ulceration 6. Known sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) or opiates 7. Hypercapnic ventilatory failure 8. Known intravenous drug abuse 9. Severe renal or liver disease 10. Known bleeding diathesis 11. Warfarin therapy which must be continued 12. Current or recent (within two weeks) corticosteroid steroid therapy
Date of first enrolment	26/03/2007
Date of final enrolment	31/12/2009

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Oxford Centre for Respiratory Medicine

Oxford
OX3 7LJ
United Kingdom

Sponsor information

University of Oxford (UK)
University/education

c/o Heather House
Head of Clinical Trials Office
University of Oxford
Manor House
John Radcliffe Hospital
Headington
Oxford
OX3 9DZ
England
United Kingdom

"ROR"	https://ror.org/052gg0110

Funders

Funder type

University/education

University of Oxford (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/12/2015		Yes	No
Plain English results			31/03/2022	No	Yes

Editorial Notes

31/03/2022: Plain English results and total final enrolment added.

On 01/05/2008 the overall trial start and end dates were updated
Previous overall trial start date: 01/09/2006
Previous overall trial end date: 01/09/2008

On 22/02/2011 the overall trial end date was updated
Previous overall trial end date: 31/12/2009