REC 06/Q0801/27

The Royal Marsden NHS Foundation Trust

Fulham Road, London, United Kingdom, SW3 6JJ

The Royal Marsden NHS Foundation Trust, The Royal Marsden NHS Foundation Trust, 44 2086426011, mary.obrien@rmh.nhs.uk

The Royal Marsden NHS Foundation Trust, The Royal Marsden NHS Foundation Trust, 44 2086425011, mary.obrien@rmh.nhs.uk

No

No

No

Final

26 Aug 2014

Yes

10 Jun 2014

Yes

21 Jul 2014

No

To investigate whether use of acupuncture in lung cancer-related breathlessness improves symptoms when compared with use of morphine

There were regular meetings to review adverse events and progress of the trial.

04 Jul 2006

No

No

United Kingdom: 173

173

173

0

0

0

0

0

0

40

124

9

Baseline

Randomised - controlled

Yes

Acupuncture

Transdermal system

Transdermal use

Acupuncture was administered to two upper sternal midline points, five paraspinal points from T1 to T5, two to three trigger points in the trapezius muscle bilaterally and LI4 (acupuncture point near the base of thumb) bilaterally. Thirty-millimetre-long 36-gauge stainless steel acupuncture needles (Seirin) were inserted and left in situ for 10 min. At sternal points, needles were inserted to the level of the periosteum and gently ‘pecked’ twice. After needle removal, stainless steel press needle studs (Seirin/Acumedic) were inserted in the upper 6 cm of the midline sternum to 0.6 mm and covered with a dressing. Treatments were given between 12 and 2 pm to avoid diurnal variation. Patients were instructed to massage studs for 1 to 2 minutees when symptomatic or prior to exercise whilst documenting in a diary. All studs were removed and the area healed before any chemotherapy was given.

Oramorph

Oral solution

Oral use

Patients will be prescribed a fixed dose of oral morphine solution (Oramorph; 10mg in 5ml) 2.5mg 4 hourly. Patients will be instructed to take their dose of morphine at 4-hour intervals, with breakthrough doses as required - not less than 1 hour after previous dose - and omission of doses if not required. Patients were given a daily diary card to document this. Patients were allowed to increase or decrease their dose of morphine if required.

Acupuncture + Morphine (Oramorph)

Oral solution

Oral use

In arm AM, patients received 2.5mg dose of morphine (same as for arm M) 20 mins before acupuncture (as for arm A). Patients were instructed to massage studs and take further doses of morphine if breathlessness persists. Daily diary cards were provided for documentation. All studs were removed and the area healed before any chemotherapy was given.

VAS Dyspnoea response at 4 hours

Randomised - controlled

Yes

Acupuncture

Transdermal system

Transdermal use

Acupuncture was administered to two upper sternal midline points, five paraspinal points from T1 to T5, two to three trigger points in the trapezius muscle bilaterally and LI4 (acupuncture point near the base of thumb) bilaterally. Thirty-millimetre-long 36-gauge stainless steel acupuncture needles (Seirin) were inserted and left in situ for 10 min. At sternal points, needles were inserted to the level of the periosteum and gently ‘pecked’ twice. After needle removal, stainless steel press needle studs (Seirin/Acumedic) were inserted in the upper 6 cm of the midline sternum to 0.6 mm and covered with a dressing. Treatments were given between 12 and 2 pm to avoid diurnal variation. Patients were instructed to massage studs for 1 to 2 minutees when symptomatic or prior to exercise whilst documenting in a diary. All studs were removed and the area healed before any chemotherapy was given.

Oramorph

Oral solution

Oral use

Patients will be prescribed a fixed dose of oral morphine solution (Oramorph; 10mg in 5ml) 2.5mg 4 hourly. Patients will be instructed to take their dose of morphine at 4-hour intervals, with breakthrough doses as required - not less than 1 hour after previous dose - and omission of doses if not required. Patients were given a daily diary card to document this. Patients were allowed to increase or decrease their dose of morphine if required.

Acupuncture + Morphine (Oramorph)

Oral solution

Oral use

In arm AM, patients received 2.5mg dose of morphine (same as for arm M) 20 mins before acupuncture (as for arm A). Patients were instructed to massage studs and take further doses of morphine if breathlessness persists. Daily diary cards were provided for documentation. All studs were removed and the area healed before any chemotherapy was given.

Acupuncture (Arm A)

Morphine (Arm M)

Acupuncture + Morphine (Arm AM)

Acupuncture (Arm A)

Morphine (Arm M)

Acupuncture + Morphine (Arm AM)

Acupuncture (Arm A)

Morphine (Arm M)

Acupuncture + Morphine (Arm AM)

Total

VAS Dyspnoea response at 4 hours

The primary endpoint of the study is dyspnoea response at 4 hours. A patient is considered to have had a dyspnoea response if they record a 1.5 or greater point reduction in the VAS for dyspnoea at 4 hours compared to baseline. Patients withdrawn before the 4 hour assessment are considered to be non-responders. Primary endpoint analysed as per intention-to-treat (ITT) population i.e. all randomised patients fulfilling the eligibility criteria (173 total).

Primary

VAS dyspnoea response at 4 hours after baseline

Proportion of responders and non-responders compared between Arm A vs. Arm M, and comparison between Arm AM vs. Arm M. Response is defined as 1.5 points (or more) reduction in VAS dyspnoea at 4 hours compared to baseline assessment. Two interim analyses were performed in 2009 & 2012. Protocol specified that trial would stop if there was sufficient evidence of a treatment effect (alpha = 0.01). As there was no significant difference in the response rate between arms, recruitment continued to 173

Acupuncture (Arm A) v Morphine (Arm M) v Acupuncture + Morphine (Arm AM)

173

Pre-specified

Adverse events including SAEs were reported from the time of informed consent and for a minimum of 28 days after stopping study medication. Toxicity data were available for 123 patients. Side-effects were in line with morphine’s toxicity profile.

In arm M, 39% of patients reported toxicity (G1) such as constipation, nausea and drowsiness. One patient withdrew due to morphine intolerance. In arm AM, 35% of patients reported toxicity, constipation (G1) being the most common (33%). One patient died of progressive lung cancer. In arm A, 1% reported toxicity (G1-2).

3