TIME1

The first therapeutic intervention in malignant pleural effusion trial

A 2 x 2 factorial trial to assess whether non-steroidal anti-inflammatory analgesics and small bore chest tubes are less painful than opiate analgesics and large bore chest tubes in pleurodesis for malignant pleural effusion

What was this study about?

Patients with cancer that has spread (metastasised) often have fluid collecting around the lung as a result of cancer cells spreading to the membranes adjacent to the lung (malignant pleural effusion). This problem affects more than 200,000 patients per year in the UK and USA combined. The standard way of treating this condition, which may cause unpleasant symptoms such as breathlessness and cough, is to drain the fluid off and then seal the cavity, using a drug (talc) given into the chest drain. Talc causes inflammation in the lining of the lung and chest wall, sticking the two surfaces together and preventing fluid from recurring. This procedure is often very painful; the pain may be partly related to the size of the chest tube used and the type of analgesia taken by the patient during the procedure. Reducing the amount of pain associated with this procedure would be a substantial benefit for patients undergoing this procedure. This trial is looking at which of two different drug regimens is more effective in preventing pleurodesis pain, and whether the size of chest tube influences pain. It will also address whether either of these influences success rate of pleurodesis.

What difference did this study make?

The TIME1 trial found that the type of painkiller used makes no difference when treating a complication of lung cancer. The study compared NSAIDs (nonsteroidal anti-inflammatory drugs) with opiates.

The results were published in JAMA on 22 December. The study looked at which type of painkiller would work best during treatment for malignant pleural effusion. It also examined if different chest tube sizes affected the level of pain. The evidence for the best method of treatment was previously poor.

Results showed that the type of painkiller had no effect on pain levels during the procedure. However, those using NSAIDs needed a small amount of extra pain medicine whilst the chest tube was in place. NSAID use also did not reduce the success of the pleurodesis three months on.

Smaller tubes lessened pain slightly for those patients who did not have thoracoscopy, but they were associated with more complications during insertion. They also resulted in higher fall out rates and a higher rate of not being able to administer talc.

The data suggested larger tubes were more effective for pleurodesis by an estimated margin of 10%. They were associated with fewer complications during insertion, less failure to give talc, and a lower proportion of falling out.

Malignant pleural effusion affects more than 300,000 patients per year, in the UK and USA combined. The study's authors believe the results challenge current guidelines. These suggest avoiding NSAIDs and using smaller chest tubes.

Type of study

Randomised trial

Contact details

ortu@ouh.nhs.uk

Who funded the study?

This trial is being funded by the Medical Research Council.

When did it take place?

TIME1 closed to recruitment on 09 October 2012.

Where did it take place?

Multiple hospitals across the UK and Internationally.

Who was included?

People who have a cancer that has spread, causing fluid to accumulate around their lungs. We recruited 320 patients.