Trial Outcomes & Findings for Self-Assessment Method for Statin Side-effects Or Nocebo (NCT NCT02668016)

Last Updated: 2024-08-07

Results Overview

The full scale name would be "daily symptom score" measuring patient-reported symptoms on a scale from 0 (no symptoms) to 100 (worst imaginable symptoms). The unit of measurement would be "scores on a scale". The mean symptom scores for the four months on each arm will be calculated: placebo, Atorvastatin 20mg and no treatment. Mean symptom scores across statin, placebo and no treatment periods is calculated. There are no subscales/subranges.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

12 months

Results posted on

2024-08-07

Participant Flow

Participant milestones

Participant milestones
Measure	All Study Participants All participants received: Atorvastatin 20mg daily taken orally for one month or placebo daily for one month or no tablets for one month. Each participant was randomised to 4 x 1-month periods of Atorvastatin 20mg daily taken orally for one month and 4 x 1-month periods of placebo daily for one month and 4 x 1 no tablets daily for one month. The 12 treatment periods could be in any order.
Month 1 STARTED	60
Month 1 Received Atorvastatin 20mg	20
Month 1 Received Placebo	20
Month 1 Received No Tablet	20
Month 1 Withdrew	0
Month 1 COMPLETED	55
Month 1 NOT COMPLETED	5
Month 2 STARTED	60
Month 2 Received Atorvastatin 20mg	20
Month 2 Received Placebo	20
Month 2 Received No Tablet	20
Month 2 Withdrew	2
Month 2 COMPLETED	54
Month 2 NOT COMPLETED	6
Month 3 STARTED	58
Month 3 Received Atorvastatin 20mg	18
Month 3 Received Placebo	20
Month 3 Received No Tablet	20
Month 3 Withdrew	0
Month 3 COMPLETED	47
Month 3 NOT COMPLETED	11
Month 4 STARTED	58
Month 4 Received Atorvastatin 20mg	19
Month 4 Received Placebo	19
Month 4 Received No Tablet	20
Month 4 Withdrew	2
Month 4 COMPLETED	53
Month 4 NOT COMPLETED	5
Month 5 STARTED	56
Month 5 Received Atorvastatin 20mg	18
Month 5 Received Placebo	19
Month 5 Received No Tablet	19
Month 5 Withdrew	0
Month 5 COMPLETED	53
Month 5 NOT COMPLETED	3
Month 6 STARTED	56
Month 6 Received Atorvastatin 20mg	19
Month 6 Received Placebo	17
Month 6 Received No Tablet	20
Month 6 Withdrew	4
Month 6 COMPLETED	50
Month 6 NOT COMPLETED	6
Month 7 STARTED	52
Month 7 Received Atorvastatin 20mg	18
Month 7 Received Placebo	18
Month 7 Received No Tablet	16
Month 7 Withdrew	0
Month 7 COMPLETED	43
Month 7 NOT COMPLETED	9
Month 8 STARTED	52
Month 8 Received Atorvastatin 20mg	18
Month 8 Received Placebo	19
Month 8 Received No Tablet	15
Month 8 Withdrew	1
Month 8 COMPLETED	45
Month 8 NOT COMPLETED	7
Month 9 STARTED	51
Month 9 Received Atorvastatin 20mg	15
Month 9 Received Placebo	19
Month 9 Received No Tablet	17
Month 9 Withdrew	0
Month 9 COMPLETED	40
Month 9 NOT COMPLETED	11
Month 10 STARTED	51
Month 10 Received Atorvastatin 20mg	15
Month 10 Received Placebo	18
Month 10 Received No Tablet	18
Month 10 Withdrew	2
Month 10 COMPLETED	43
Month 10 NOT COMPLETED	8
Month 11 STARTED	49
Month 11 Received Atorvastatin 20mg	17
Month 11 Received Placebo	15
Month 11 Received No Tablet	17
Month 11 Withdrew	0
Month 11 COMPLETED	42
Month 11 NOT COMPLETED	7
Month 12 STARTED	49
Month 12 Received Atorvastatin 20mg	16
Month 12 Received Placebo	17
Month 12 Received No Tablet	16
Month 12 Withdrew	0
Month 12 COMPLETED	43
Month 12 NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	All Study Participants All participants received: Atorvastatin 20mg daily taken orally for one month or placebo daily for one month or no tablets for one month. Each participant was randomised to 4 x 1-month periods of Atorvastatin 20mg daily taken orally for one month and 4 x 1-month periods of placebo daily for one month and 4 x 1 no tablets daily for one month. The 12 treatment periods could be in any order.
Month 2 Withdrew due to other health condition preventing continuation with the protocol	1
Month 2 Withdrew due to repeated failure to provide treatment scores	1
Month 2 Not applicable - stopped trial medication for rest of month but continued in the trial	4
Month 4 Withdrawal due to severe symptoms	1
Month 4 Withdrawal due to non-compliance with trial protocol	1
Month 4 Not applicable - stopped trial medication for rest of month but continued in the trial	3
Month 6 Withdrawal as decided side effects non longer statin mediated	1
Month 6 Withdrawal due to severe symptoms	2
Month 6 Withdrawal due to other health issues preventing continuation with the protocol	1
Month 6 Not applicable - stopped trial medication for rest of month but continued in the trial	2
Month 8 Withdrawal due to severe symptoms	1
Month 8 Not applicable - stopped trial medication for rest of month but continued in the trial	6
Month 10 Withdrawal due to intercurrent social stresses	1
Month 10 Withdrawal due to severe symptoms	1
Month 10 Not applicable - stopped trial medication for rest of month but continued in the trial	6

Baseline Characteristics

Self-Assessment Method for Statin Side-effects Or Nocebo

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atorvastatin 20mg Daily n=60 Participants Atorvastatin 20mg daily for 1 month or Placebo daily or No Treatment
Age, Continuous	65.5 Years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United Kingdom	60 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Crossover trial - The primary end point was symptom intensity as assessed with the use of the nocebo ratio (i.e., the ratio of symptom intensity induced by taking placebo to the symptom intensity induced by taking a statin). This ratio was calculated as the symptom intensity with placebo minus the symptom intensity with neither statin nor placebo, divided by the symptom intensity with a statin minus the symptom intensity with neither statin nor placebo.

Outcome measures

Outcome measures
Measure	Atorvastatin 20mg Daily n=60 Participants Atorvastatin 20mg daily for 1 month Atorvastatin: Atorvastatin 20mg tablets taken orally once daily for one month.	Placebo n=60 Participants Placebo daily for 1 month Placebo: Placebo tablets taken orally once daily for one month	No Treatment n=60 Participants No Atorvastatin or placebo for 1 month
Mean Symptom Scores Across Statin, Placebo and no Treatment Periods	16.3 units on a scale Interval 13.0 to 19.6	15.4 units on a scale Interval 12.1 to 18.7	8.0 units on a scale Interval 4.7 to 11.3

SECONDARY outcome

Timeframe: At 6-months after the end of trial up to 7-months

Population: Cross-over design

Following the end of the trial, is the trial participant taking statins or not.

Outcome measures

Outcome measures
Measure	Atorvastatin 20mg Daily n=60 Participants Atorvastatin 20mg daily for 1 month Atorvastatin: Atorvastatin 20mg tablets taken orally once daily for one month.	Placebo Placebo daily for 1 month Placebo: Placebo tablets taken orally once daily for one month	No Treatment No Atorvastatin or placebo for 1 month
Number of Participants Currently Being Prescribed Statins	30 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 6-months after end of trial

Following the end of the trial, whether individual trial participants currently believe that most of the side-effects previously attributed to the statin, were indeed a pharmacological effect of the statin.

Outcome measures

Outcome measures
Measure	Atorvastatin 20mg Daily n=60 Participants Atorvastatin 20mg daily for 1 month Atorvastatin: Atorvastatin 20mg tablets taken orally once daily for one month.	Placebo Placebo daily for 1 month Placebo: Placebo tablets taken orally once daily for one month	No Treatment No Atorvastatin or placebo for 1 month
Attribution of Adverse Symptoms Unknown	8 participants	—	—
Attribution of Adverse Symptoms Other	3 participants	—	—
Attribution of Adverse Symptoms Undecided	9 participants	—	—
Attribution of Adverse Symptoms Lost to follow-up	1 participants	—	—
Attribution of Adverse Symptoms Yes	22 participants	—	—
Attribution of Adverse Symptoms No	17 participants	—	—

Adverse Events

Atorvastatin 20mg Daily

Serious events: 5 serious events

Other events: 36 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 42 other events

Deaths: 0 deaths

No Treatment

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

In-Follow-up

Serious events: 10 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Atorvastatin 20mg Daily n=60 participants at risk Atorvastatin 20mg daily for 1 month Atorvastatin: Atorvastatin 20mg tablets taken orally once daily for one month.	Placebo n=60 participants at risk Placebo daily for 1 month Placebo: Placebo tablets taken orally once daily for one month	No Treatment n=60 participants at risk No Atorvastatin or placebo for 1 month	In-Follow-up n=60 participants at risk Completed or withdrawn from trial intervention but in follow-up until end of trial +6-month follow-up visit.
Musculoskeletal and connective tissue disorders Myalgia	35.0% 21/60 • Number of events 39 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	38.3% 23/60 • Number of events 33 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	5.0% 3/60 • Number of events 3 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • Number of events 1 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	15.0% 9/60 • Number of events 9 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	25.0% 15/60 • Number of events 19 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	15.0% 9/60 • Number of events 12 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • Number of events 1 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
General disorders Fatigue	16.7% 10/60 • Number of events 13 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	20.0% 12/60 • Number of events 15 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	5.0% 3/60 • Number of events 3 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Musculoskeletal and connective tissue disorders Arthralgia	13.3% 8/60 • Number of events 14 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	10.0% 6/60 • Number of events 6 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	3.3% 2/60 • Number of events 2 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	5.0% 3/60 • Number of events 3 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Musculoskeletal and connective tissue disorders Muscle Spasms	10.0% 6/60 • Number of events 6 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	13.3% 8/60 • Number of events 11 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • Number of events 1 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • Number of events 1 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Psychiatric disorders Sleep disorder	11.7% 7/60 • Number of events 7 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	8.3% 5/60 • Number of events 6 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • Number of events 1 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Respiratory, thoracic and mediastinal disorders Cough	3.3% 2/60 • Number of events 2 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	13.3% 8/60 • Number of events 9 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • Number of events 1 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Gastrointestinal disorders Diarrhoea	3.3% 2/60 • Number of events 4 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	6.7% 4/60 • Number of events 4 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	6.7% 4/60 • Number of events 4 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Nervous system disorders Headache	10.0% 6/60 • Number of events 7 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	5.0% 3/60 • Number of events 3 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • Number of events 1 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Injury, poisoning and procedural complications Fall	1.7% 1/60 • Number of events 1 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	8.3% 5/60 • Number of events 5 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	3.3% 2/60 • Number of events 2 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • Number of events 1 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 4/60 • Number of events 4 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	8.3% 5/60 • Number of events 5 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.

Additional Information

Professor Darrel Francis

Imperial College London

Phone: 0207 594 9647

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Atorvastatin 20mg Daily n=60 participants at risk Atorvastatin 20mg daily for 1 month Atorvastatin: Atorvastatin 20mg tablets taken orally once daily for one month.	Placebo n=60 participants at risk Placebo daily for 1 month Placebo: Placebo tablets taken orally once daily for one month	No Treatment n=60 participants at risk No Atorvastatin or placebo for 1 month	In-Follow-up n=60 participants at risk Completed or withdrawn from trial intervention but in follow-up until end of trial +6-month follow-up visit.
Blood and lymphatic system disorders Polycythemia	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Gastrointestinal disorders Obstructive Pancreatitis	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Infections and infestations Urinary tract infection	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Infections and infestations Influenza	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Infections and infestations Sepsis	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Injury, poisoning and procedural complications Hemoperitoneum	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Metabolism and nutrition disorders Iron Deficiency	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Reproductive system and breast disorders Breast Cancer	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Surgical and medical procedures Tonsillectomy	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Surgical and medical procedures Cardiopulmonary bypass	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Surgical and medical procedures Shoulder Arthroplasty	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Surgical and medical procedures Transurethral prostatectomy	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Vascular disorders Transient Ischaemic Attack	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.
Vascular disorders Myocardial Infarction	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	0.00% 0/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.	1.7% 1/60 • 12-months of the trial and for six-months post-trial until the participant had completed their end of study plus six-month visit. Definition of adverse events does not differ to clinicaltrials.gov.