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A Randomised, Placebo-Controlled, Crossover Trial of Acetaminophen in Cancer Patients on Strong Opioids

Phase 3
18 Years
Open (Enrolling)
Cancer, Pain

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Trial Information

A Randomised, Placebo-Controlled, Crossover Trial of Acetaminophen in Cancer Patients on Strong Opioids


To assess whether regular oral acetaminophen can reduce pain in cancer patients already on a
strong opioid regimen.


It is estimated that 75% of people with advanced cancer suffer significant pain. Many of
these people continue to have pain despite being on strong opioids. The rationale behind
adding an additional analgesic with a different mechanism of action is to attempt to improve
analgesia without increasing side effects.


This is a double blind, randomised placebo-controlled, crossover trial to evaluate whether
the addition of regular acetaminophen can reduce pain in cancer patients already on a strong
opioid regimen. The study will be performed in ambulatory cancer patients who have pain
that is believed to be caused by their cancer, and who have already been stabilised on an
opioid regimen of > 60mg/day of morphine equivalents. Each patient will be randomly
allocated to receive either acetaminophen 1g qid or an identical appearing placebo qid for a
seven-day period, and then crossed over to the other arm for a further seven-day period.
Patients will complete daily pain diaries and weekly questionnaires (Brief Pain Inventory)
and comparison will be made between the pain scores for the two treatment periods. Patient
preference for the two treatment periods will also be evaluated.

Research Question:

A randomised, double-blind, placebo controlled crossover trial to determine if the addition
of regular acetaminophen (1g PO qid) leads to improved analgesic control in adult cancer
patients at Princess Margaret Hospital, who are already on strong opioids (> 60mg morphine
equivalents/day) as evaluated by daily pain scores measured by Numerical Rating Scales (NRS)
and the Brief Pain Inventory (BPI).


Regular acetaminophen improves pain control in cancer patients who are already on strong
opioid regimens.

Inclusion Criteria:

1. Patients diagnosed with malignancy who have persistent pain which is believed by the
investigator to be due to their cancer, and whose analgesic regimen has been
stabilised on > 60mg of morphine equivalents/day.

2. Age > 18 years

3. Performance status of 0-2 by the European Co-operative Oncology Group (ECOG)
Performance Scale

4. Sufficient English skills to be able to complete the daily diary, BPI and to
understand the consent form

5. Signed informed consent

Exclusion Criteria:

1. Patient has no pain (0/10 on NRS).

2. Patients with severe pain are excluded, however once their pain control is optimised
they are eligible.

3. Patient has received radiation therapy in the six weeks prior to commencing the study
or is likely to require radiotherapy during the study period.

4. Patient has commenced, or had dose modifications, to either non-steroidal
anti-inflammatory drugs (NSAIDs) or corticosteroids in the week prior to commencing
the study, or during the two-week study period.

5. Patient has commenced chemotherapy or hormone therapy in the 4 weeks prior to the
study or is expected to commence chemotherapy or hormonotherapy during the study
period. Patients who are stable on long-term chemotherapy or hormones are eligible
for this study. Patients who receive high dose steroids as antiemetics with their
chemotherapy are eligible providing they are not receiving the steroids during the
study period.

6. Patient has a contraindication to acetaminophen.

7. Use of acetaminophen in the 48 hours prior to commencement of the study period.

8. Abnormal laboratory values:

- Absolute neutrophil count < 1.5 X 10^9/L and white blood cell (WBC) count < 3 X

- Platelet count < 100 X 10^9/L

- Liver transaminases > 2.5 X upper limit of normal

- Bilirubin > 1.5 X upper limit of normal

- Creatinine > 1.5 X upper limit of normal

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Patient preference for the acetaminophen or the placebo arm as assessed by asking the patient whether he/she preferred treatment period 1 or treatment period 2

Outcome Time Frame:

Post completion of period 2

Safety Issue:


Principal Investigator

Janette Vardy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network, University of Toronto


Canada: Health Canada

Study ID:




Start Date:

July 2005

Completion Date:

December 2012

Related Keywords:

  • Cancer
  • Pain
  • cancer pain
  • acetaminophen
  • opioids