Trial Outcomes & Findings for Trial Of Irinotecan In Combination With Three Methods Of Administration Of Fluoropyrimidine. (NCT NCT00101686)
NCT ID: NCT00101686
Last Updated: 2010-01-12
Results Overview
Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
547 participants
Primary outcome timeframe
every 6 weeks until disease progression
Results posted on
2010-01-12
Participant Flow
Participant milestones
| Measure |
FOLFIRI + Celecoxib
Irinotecan plus infusional 5-Fluorouracil(5-FU)/Leucovorin(LV) (FOLFIRI) with celecoxib
|
FOLFIRI + Placebo
Irinotecan plus infusional 5-FU/LV (FOLFIRI) with placebo
|
mIFL + Celecoxib
Modified irinotecan plus bolus 5-FU/LV (mIFL) with celecoxib
|
mIFL + Placebo
Modified irinotecan plus bolus 5-FU/LV (mIFL) with placebo
|
CapeIRI + Celecoxib
Irinotecan plus capecitabine (CapeIRI) with celecoxib
|
CapeIRI + Placebo
Irinotecan plus capecitabine (CapeIRI) with placebo
|
Bevacizumab + FOLFIRI + Celecoxib
Bevacizumab + Irinotecan plus infusional 5-FU/LV (FOLFIRI) with celecoxib
|
Bevacizumab + FOLFIRI + Placebo
Bevacizumab + Irinotecan plus infusional 5-FU/LV (FOLFIRI) with placebo
|
Bevacizumab + mIFL + Celecoxib
Bevacizumab + Modified irinotecan plus bolus 5-FU/LV (mIFL) with celecoxib
|
Bevacizumab + mIFL + Placebo
Bevacizumab + Modified irinotecan plus bolus 5-FU/LV (mIFL)with placebo
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
71
|
73
|
69
|
72
|
73
|
72
|
27
|
30
|
30
|
30
|
|
Overall Study
Received Treatment
|
70
|
67
|
67
|
70
|
71
|
70
|
27
|
29
|
30
|
29
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
71
|
73
|
69
|
72
|
73
|
72
|
27
|
30
|
30
|
30
|
Reasons for withdrawal
| Measure |
FOLFIRI + Celecoxib
Irinotecan plus infusional 5-Fluorouracil(5-FU)/Leucovorin(LV) (FOLFIRI) with celecoxib
|
FOLFIRI + Placebo
Irinotecan plus infusional 5-FU/LV (FOLFIRI) with placebo
|
mIFL + Celecoxib
Modified irinotecan plus bolus 5-FU/LV (mIFL) with celecoxib
|
mIFL + Placebo
Modified irinotecan plus bolus 5-FU/LV (mIFL) with placebo
|
CapeIRI + Celecoxib
Irinotecan plus capecitabine (CapeIRI) with celecoxib
|
CapeIRI + Placebo
Irinotecan plus capecitabine (CapeIRI) with placebo
|
Bevacizumab + FOLFIRI + Celecoxib
Bevacizumab + Irinotecan plus infusional 5-FU/LV (FOLFIRI) with celecoxib
|
Bevacizumab + FOLFIRI + Placebo
Bevacizumab + Irinotecan plus infusional 5-FU/LV (FOLFIRI) with placebo
|
Bevacizumab + mIFL + Celecoxib
Bevacizumab + Modified irinotecan plus bolus 5-FU/LV (mIFL) with celecoxib
|
Bevacizumab + mIFL + Placebo
Bevacizumab + Modified irinotecan plus bolus 5-FU/LV (mIFL)with placebo
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Progressive Disease
|
37
|
28
|
37
|
38
|
28
|
25
|
5
|
7
|
10
|
8
|
|
Overall Study
initiation other anti-cancer treatment
|
4
|
3
|
4
|
3
|
1
|
1
|
2
|
2
|
3
|
3
|
|
Overall Study
>3 week delay treatment due toxicity
|
6
|
2
|
1
|
2
|
7
|
3
|
2
|
1
|
3
|
0
|
|
Overall Study
unacceptable toxicity
|
3
|
9
|
10
|
6
|
16
|
10
|
4
|
2
|
1
|
4
|
|
Overall Study
Randomized but did not receive treament
|
1
|
6
|
2
|
2
|
2
|
2
|
0
|
1
|
0
|
1
|
|
Overall Study
intercurrent non-cancer related illness
|
0
|
0
|
2
|
0
|
1
|
3
|
1
|
0
|
1
|
1
|
|
Overall Study
Physician Decision
|
10
|
13
|
6
|
7
|
8
|
9
|
5
|
5
|
1
|
1
|
|
Overall Study
Other
|
1
|
4
|
1
|
6
|
2
|
12
|
1
|
5
|
3
|
3
|
|
Overall Study
Withdrawal by Subject
|
9
|
8
|
6
|
8
|
8
|
7
|
7
|
7
|
8
|
9
|
Baseline Characteristics
Trial Of Irinotecan In Combination With Three Methods Of Administration Of Fluoropyrimidine.
Baseline characteristics by cohort
| Measure |
FOLFIRI + Celecoxib
n=71 Participants
Irinotecan plus infusional 5-Fluorouracil(5-FU)/Leucovorin(LV) (FOLFIRI) with celecoxib
|
FOLFIRI + Placebo
n=73 Participants
Irinotecan plus infusional 5-FU/LV (FOLFIRI) with placebo
|
mIFL + Celecoxib
n=69 Participants
Modified irinotecan plus bolus 5-FU/LV (mIFL) with celecoxib
|
mIFL + Placebo
n=72 Participants
Modified irinotecan plus bolus 5-FU/LV (mIFL) with placebo
|
CapeIRI + Celecoxib
n=73 Participants
Irinotecan plus capecitabine (CapeIRI) with celecoxib
|
CapeIRI + Placebo
n=72 Participants
Irinotecan plus capecitabine (CapeIRI) with placebo
|
Bevacizumab + FOLFIRI + Celecoxib
n=27 Participants
Bevacizumab + Irinotecan plus infusional 5-FU/LV (FOLFIRI) with celecoxib
|
Bevacizumab + FOLFIRI + Placebo
n=30 Participants
Bevacizumab + Irinotecan plus infusional 5-FU/LV (FOLFIRI) with placebo
|
Bevacizumab + mIFL + Celecoxib
n=30 Participants
Bevacizumab + Modified irinotecan plus bolus 5-FU/LV (mIFL) with celecoxib
|
Bevacizumab + mIFL + Placebo
n=30 Participants
Bevacizumab + Modified irinotecan plus bolus 5-FU/LV (mIFL)with placebo
|
Total
n=547 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
29 Participants
n=21 Participants
|
37 Participants
n=8 Participants
|
13 Participants
n=8 Participants
|
14 Participants
n=24 Participants
|
10 Participants
n=42 Participants
|
12 Participants
n=42 Participants
|
225 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
49 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
48 Participants
n=4 Participants
|
44 Participants
n=21 Participants
|
35 Participants
n=8 Participants
|
14 Participants
n=8 Participants
|
16 Participants
n=24 Participants
|
20 Participants
n=42 Participants
|
18 Participants
n=42 Participants
|
322 Participants
n=42 Participants
|
|
Age Continuous
|
61.0 years
n=5 Participants
|
62.0 years
n=7 Participants
|
61.0 years
n=5 Participants
|
62.0 years
n=4 Participants
|
62.0 years
n=21 Participants
|
62.5 years
n=8 Participants
|
59.0 years
n=8 Participants
|
59.5 years
n=24 Participants
|
61.0 years
n=42 Participants
|
59.0 years
n=42 Participants
|
61.0 years
n=42 Participants
|
PRIMARY outcome
Timeframe: every 6 weeks until disease progressionPopulation: Intent-to-Treat Population (ITT) - all subjects who were randomized, with study drug assignment designated according to initial randomization, regardless of whether subjects received any study drug or received a different drug from that to which they were randomized.
Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).
Outcome measures
| Measure |
FOLFIRI
n=144 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=141 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL
|
8.18 months
Interval 7.43 to 8.97
|
6.01 months
Interval 5.52 to 7.03
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: every 6 weeks until disease progressionPopulation: ITT Population.
Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).
Outcome measures
| Measure |
FOLFIRI
n=144 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=141 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
n=145 Participants
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Time to Progression: FOLFIRI, mIFL and CapeIRI
|
7.62 months
Interval 7.06 to 8.71
|
5.98 months
Interval 5.45 to 6.9
|
5.82 months
Interval 4.6 to 6.9
|
—
|
—
|
SECONDARY outcome
Timeframe: every 6 weeks during chemotherapy until disease progressionPopulation: ITT Population.
A subject will be considered achieving an overall response if the subject has a sustained Complete Response (CR) or Partial Response (PR) for at least 4 weeks, confirmed by tumor assessments. (CR: Disappearance of all target lesions. PR: greater than or equal to 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the Pre-treatment sum LD. )
Outcome measures
| Measure |
FOLFIRI
n=144 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=141 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
n=145 Participants
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Overall Response: FOLFIRI, mIFL and CapeIRI
|
68 participants
|
61 participants
|
56 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: assessed at least every week during treatment and at least every 3 months during follow-upPopulation: ITT Population.
Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.
Outcome measures
| Measure |
FOLFIRI
n=144 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=141 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
n=145 Participants
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Survival Time: FOLFIRI, mIFL and CapeIRI
|
23.06 months
Interval 17.87 to 26.55
|
17.64 months
Interval 14.29 to 23.03
|
18.92 months
Interval 15.74 to 23.23
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 year from date of randomizationPopulation: ITT Population.
Number of patients alive or dead at 1 year. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.
Outcome measures
| Measure |
FOLFIRI
n=144 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=141 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
n=145 Participants
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
1 Year Survival: FOLFIRI, mIFL and CapeIRI
Dead at 1 year
|
34 participants
|
47 participants
|
46 participants
|
—
|
—
|
|
1 Year Survival: FOLFIRI, mIFL and CapeIRI
Alive at 1 year
|
101 participants
|
86 participants
|
89 participants
|
—
|
—
|
|
1 Year Survival: FOLFIRI, mIFL and CapeIRI
Censored
|
9 participants
|
8 participants
|
10 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: every 6 weeks until disease progressionPopulation: ITT Population. Celecoxib participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab); Placebo participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab).
Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).
Outcome measures
| Measure |
FOLFIRI
n=213 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=217 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Time to Progression : Celecoxib and Placebo
|
6.64 months
Interval 5.68 to 7.39
|
6.70 months
Interval 6.01 to 7.26
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: every 6 weeks during chemotherapy until disease progressionPopulation: ITT Population. Celecoxib participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab); Placebo participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab).
A subject will be considered achieving an overall response if the subject has a sustained CR or PR for at least 4 weeks, confirmed by tumor assessments. (Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥ 30% decrease in the sum of the LD of target lesions, taking as reference the Pre-treatment sum LD. )
Outcome measures
| Measure |
FOLFIRI
n=213 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=217 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Overall Response: Celecoxib and Placebo
|
84 participants
|
101 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: assessed at least every week during treatment and at least every 3 months during follow-upPopulation: ITT Population. Celecoxib participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab); Placebo participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab).
Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.
Outcome measures
| Measure |
FOLFIRI
n=213 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=217 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Survival Time: Celecoxib and Placebo
|
21.06 months
Interval 16.92 to 24.28
|
18.83 months
Interval 16.26 to 22.93
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: every 6 weeks until disease progressionPopulation: ITT population.
Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).
Outcome measures
| Measure |
FOLFIRI
n=57 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=60 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Time to Progression: Bevacizumab With FOLFIRI, mIFL
|
11.17 months
Interval 9.0 to 17.41
|
8.31 months
Interval 6.31 to 11.63
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: every 6 weeks during chemotherapy until disease progressionPopulation: ITT population.
A subject will be considered achieving an overall response if the subject has a sustained CR or PR for at least 4 weeks, confirmed by tumor assessments. (Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥ 30% decrease in the sum of the LD of target lesions, taking as reference the Pre-treatment sum LD. )
Outcome measures
| Measure |
FOLFIRI
n=57 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=60 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Overall Response: Bevacizumab With FOLFIRI, mIFL
|
33 participants
|
32 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 year from date of randomizationPopulation: ITT Population.
Number of patients alive or dead at 1 year. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.
Outcome measures
| Measure |
FOLFIRI
n=57 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=60 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
1 Year Survival: Bevacizumab With FOLFIRI, mIFL
Alive at 1 year
|
45 participants
|
33 participants
|
—
|
—
|
—
|
|
1 Year Survival: Bevacizumab With FOLFIRI, mIFL
Dead at 1 year
|
7 participants
|
22 participants
|
—
|
—
|
—
|
|
1 Year Survival: Bevacizumab With FOLFIRI, mIFL
Censored
|
5 participants
|
5 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Last Follow-Up VisitPopulation: ITT Population.
Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive. Zero subjects analyzed indicates median could not be analyzed based on number of subjects who died.
Outcome measures
| Measure |
FOLFIRI
n=57 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=60 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Survival Time at Last Follow-Up Visit: Bevacizumab With FOLFIRI, mIFL
|
27.99 months
Interval 23.82 to 34.76
|
19.22 months
Interval 11.6 to 22.28
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1; Day 8; and at end of every 3 treatment cycles for FOLFIRI; end of every 2 cycles for mIRIPopulation: As-Treated population - all subjects who received any study medication, with treatment assignments designated according to actual study treatment received.
Number of subjects that had at least one Treatment-Emergent Adverse Event (TEAE) that led to a dose reduction. TEAE includes all reported Adverse Events that occurred within 30 days of last study medication.
Outcome measures
| Measure |
FOLFIRI
n=137 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=137 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
n=141 Participants
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
n=56 Participants
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
n=59 Participants
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Dose Reduction Due to Treatment Emergent Adverse Events
|
18 participants
|
14 participants
|
39 participants
|
6 participants
|
8 participants
|
SECONDARY outcome
Timeframe: End of treatment cyclePopulation: As-Treated population
Relative dose intensity for a cycle was calculated as the percentage of the actual dose intensity of the cycle divided by the planned dose intensity of the cycle. Overall relative dose intensity was calculated as the average relative dose intensities over all cycles. (Dose intensity for each cycle was calculated as the actual dose level of the study medication received in that cycle divided by the number of weeks in the cycle.)
Outcome measures
| Measure |
FOLFIRI
n=137 Participants
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=137 Participants
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
n=145 Participants
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
n=56 Participants
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
n=59 Participants
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Overall Relative Dose Intensity of Irinotecan
|
93.9 percent dose intensity
Standard Error 0.6
|
94.5 percent dose intensity
Standard Error 0.6
|
93.8 percent dose intensity
Standard Error 0.7
|
93.3 percent dose intensity
Standard Error 0.8
|
95.5 percent dose intensity
Standard Error 0.8
|
Adverse Events
FOLFIRI
Serious events: 50 serious events
Other events: 135 other events
Deaths: 0 deaths
mIFL
Serious events: 52 serious events
Other events: 137 other events
Deaths: 0 deaths
CapeIRI
Serious events: 78 serious events
Other events: 140 other events
Deaths: 0 deaths
Bevacizumab + FOLFIRI
Serious events: 19 serious events
Other events: 56 other events
Deaths: 0 deaths
Bevacizumab + mIRI
Serious events: 21 serious events
Other events: 58 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
FOLFIRI
n=137 participants at risk
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=137 participants at risk
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
n=141 participants at risk
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
n=56 participants at risk
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
n=59 participants at risk
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.9%
4/137
|
8.8%
12/137
|
5.7%
8/141
|
5.4%
3/56
|
1.7%
1/59
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Cardiac disorders
Arteriospasm coronary
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Cardiac disorders
Atrial fibrillation
|
0.73%
1/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
3.4%
2/59
|
|
Cardiac disorders
Myocardial infarction
|
0.73%
1/137
|
2.9%
4/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal pain
|
3.6%
5/137
|
0.73%
1/137
|
4.3%
6/141
|
8.9%
5/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal strangulated hernia
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/137
|
1.5%
2/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Colitis
|
0.73%
1/137
|
0.00%
0/137
|
1.4%
2/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Colonic obstruction
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Constipation
|
0.73%
1/137
|
1.5%
2/137
|
0.00%
0/141
|
5.4%
3/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Diarrhoea
|
4.4%
6/137
|
5.8%
8/137
|
29.8%
42/141
|
3.6%
2/56
|
6.8%
4/59
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.73%
1/137
|
0.73%
1/137
|
1.4%
2/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Gastrointestinal hypomotility
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Gastrointestinal oedema
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Ileus
|
1.5%
2/137
|
1.5%
2/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.73%
1/137
|
0.73%
1/137
|
3.5%
5/141
|
3.6%
2/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Nausea
|
0.73%
1/137
|
3.6%
5/137
|
14.2%
20/141
|
8.9%
5/56
|
5.1%
3/59
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
1.5%
2/137
|
2.2%
3/137
|
5.0%
7/141
|
3.6%
2/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/137
|
0.00%
0/137
|
1.4%
2/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Vomiting
|
3.6%
5/137
|
4.4%
6/137
|
17.0%
24/141
|
8.9%
5/56
|
3.4%
2/59
|
|
General disorders
Asthenia
|
0.00%
0/137
|
1.5%
2/137
|
1.4%
2/141
|
0.00%
0/56
|
1.7%
1/59
|
|
General disorders
Catheter site pain
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
General disorders
Chest pain
|
1.5%
2/137
|
0.00%
0/137
|
0.71%
1/141
|
3.6%
2/56
|
3.4%
2/59
|
|
General disorders
Fatigue
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
General disorders
General physical health deterioration
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
General disorders
Oedema
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
General disorders
Oedema peripheral
|
0.73%
1/137
|
1.5%
2/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
General disorders
Pain
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
1.7%
1/59
|
|
General disorders
Pyrexia
|
3.6%
5/137
|
2.9%
4/137
|
1.4%
2/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Immune system disorders
Drug hypersensitivity
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Immune system disorders
Hypersensitivity
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Abdominal wall abscess
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Bacteraemia
|
1.5%
2/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Catheter related infection
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Infections and infestations
Cellulitis
|
1.5%
2/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Central line infection
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Device related infection
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Escherichia sepsis
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Infection
|
0.00%
0/137
|
1.5%
2/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Influenza
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Pneumonia
|
0.00%
0/137
|
1.5%
2/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Infections and infestations
Pyelonephritis
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Sepsis
|
0.73%
1/137
|
0.73%
1/137
|
0.71%
1/141
|
1.8%
1/56
|
1.7%
1/59
|
|
Infections and infestations
Staphylococcal infection
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Systemic candida
|
0.00%
0/137
|
1.5%
2/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/137
|
1.5%
2/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Injury, poisoning and procedural complications
Fall
|
0.73%
1/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Injury, poisoning and procedural complications
Polytraumatism
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Investigations
Culture stool positive
|
0.00%
0/137
|
1.5%
2/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Anorexia
|
2.9%
4/137
|
0.00%
0/137
|
2.1%
3/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Dehydration
|
3.6%
5/137
|
5.1%
7/137
|
17.0%
24/141
|
7.1%
4/56
|
1.7%
1/59
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.00%
0/137
|
0.00%
0/137
|
1.4%
2/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/137
|
1.5%
2/137
|
1.4%
2/141
|
3.6%
2/56
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
2.2%
3/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Nervous system disorders
Convulsion
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Nervous system disorders
Dizziness
|
1.5%
2/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Nervous system disorders
Syncope
|
0.73%
1/137
|
0.00%
0/137
|
1.4%
2/141
|
1.8%
1/56
|
1.7%
1/59
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/137
|
0.73%
1/137
|
2.1%
3/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Psychiatric disorders
Depression suicidal
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Renal and urinary disorders
Obstructive uropathy
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Renal and urinary disorders
Renal failure
|
0.73%
1/137
|
0.73%
1/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Renal and urinary disorders
Renal vein thrombosis
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.5%
2/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.5%
2/137
|
5.8%
8/137
|
5.7%
8/141
|
3.6%
2/56
|
3.4%
2/59
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Vascular disorders
Deep vein thrombosis
|
3.6%
5/137
|
3.6%
5/137
|
2.8%
4/141
|
3.6%
2/56
|
1.7%
1/59
|
|
Vascular disorders
Embolism
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Vascular disorders
Hypertension
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Vascular disorders
Hypotension
|
0.73%
1/137
|
0.73%
1/137
|
0.71%
1/141
|
1.8%
1/56
|
1.7%
1/59
|
|
Vascular disorders
Orthostatic hypotension
|
0.73%
1/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Vascular disorders
Peripheral ischaemia
|
0.00%
0/137
|
0.00%
0/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Vascular disorders
Thrombosis
|
1.5%
2/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Splenic infarction
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Eye disorders
Blindness
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Duodenal obstruction
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Oesophageal spasm
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Oesophageal ulcer
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
General disorders
Mucosal inflammation
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Hepatobiliary disorders
Bile duct stenosis
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Hepatobiliary disorders
Gallbladder obstruction
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Incision site complication
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Procedural site reaction
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Investigations
Transaminases increased
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
1.7%
1/59
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Monarthritis
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
0.00%
0/59
|
|
Renal and urinary disorders
Urinoma
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Alveolitis
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
1.7%
1/59
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
|
Vascular disorders
Jugular vein thrombosis
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
0.00%
0/56
|
1.7%
1/59
|
Other adverse events
| Measure |
FOLFIRI
n=137 participants at risk
Irinotecan + infusional 5-FU/LV with celecoxib or placebo
|
mIFL
n=137 participants at risk
Irinotecan + modified-bolus 5-FU/LV with celecoxib or placebo
|
CapeIRI
n=141 participants at risk
Irinotecan + oral capecitabine with celecoxib or placebo
|
Bevacizumab + FOLFIRI
n=56 participants at risk
Bevacizumab + Irinotecan + infusional 5-FU/LV with (celecoxib or placebo)
|
Bevacizumab + mIRI
n=59 participants at risk
Bevacizumab + Irinotecan + modified-bolus 5-FU/LV with (celecoxib or placebo)
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
24.8%
34/137
|
13.9%
19/137
|
11.3%
16/141
|
17.9%
10/56
|
16.9%
10/59
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
19.0%
26/137
|
10.2%
14/137
|
1.4%
2/141
|
37.5%
21/56
|
27.1%
16/59
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
7.3%
10/137
|
7.3%
10/137
|
5.7%
8/141
|
8.9%
5/56
|
10.2%
6/59
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.8%
8/137
|
3.6%
5/137
|
4.3%
6/141
|
8.9%
5/56
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
6.6%
9/137
|
4.4%
6/137
|
4.3%
6/141
|
16.1%
9/56
|
8.5%
5/59
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.2%
3/137
|
7.3%
10/137
|
5.7%
8/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
9.5%
13/137
|
4.4%
6/137
|
2.8%
4/141
|
10.7%
6/56
|
5.1%
3/59
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
46.7%
64/137
|
41.6%
57/137
|
43.3%
61/141
|
37.5%
21/56
|
18.6%
11/59
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.0%
11/137
|
5.1%
7/137
|
4.3%
6/141
|
23.2%
13/56
|
6.8%
4/59
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
10.9%
15/137
|
5.8%
8/137
|
6.4%
9/141
|
3.6%
2/56
|
8.5%
5/59
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
10.2%
14/137
|
5.1%
7/137
|
47.5%
67/141
|
21.4%
12/56
|
1.7%
1/59
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.3%
10/137
|
3.6%
5/137
|
4.3%
6/141
|
8.9%
5/56
|
6.8%
4/59
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.6%
20/137
|
12.4%
17/137
|
15.6%
22/141
|
28.6%
16/56
|
11.9%
7/59
|
|
Vascular disorders
Deep vein thrombosis
|
12.4%
17/137
|
8.0%
11/137
|
7.8%
11/141
|
8.9%
5/56
|
3.4%
2/59
|
|
Vascular disorders
Flushing
|
10.9%
15/137
|
3.6%
5/137
|
2.8%
4/141
|
5.4%
3/56
|
3.4%
2/59
|
|
Vascular disorders
Hot flush
|
7.3%
10/137
|
3.6%
5/137
|
3.5%
5/141
|
8.9%
5/56
|
6.8%
4/59
|
|
Vascular disorders
Hypertension
|
5.1%
7/137
|
2.2%
3/137
|
2.1%
3/141
|
21.4%
12/56
|
20.3%
12/59
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.1%
7/137
|
12.4%
17/137
|
7.1%
10/141
|
5.4%
3/56
|
1.7%
1/59
|
|
Ear and labyrinth disorders
Vertigo
|
5.8%
8/137
|
2.2%
3/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Eye disorders
Lacrimation increased
|
8.8%
12/137
|
2.9%
4/137
|
11.3%
16/141
|
12.5%
7/56
|
5.1%
3/59
|
|
Eye disorders
Vision blurred
|
5.1%
7/137
|
3.6%
5/137
|
5.0%
7/141
|
1.8%
1/56
|
6.8%
4/59
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.1%
7/137
|
1.5%
2/137
|
1.4%
2/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal distension
|
3.6%
5/137
|
8.0%
11/137
|
5.0%
7/141
|
5.4%
3/56
|
6.8%
4/59
|
|
Gastrointestinal disorders
Abdominal pain
|
47.4%
65/137
|
36.5%
50/137
|
43.3%
61/141
|
35.7%
20/56
|
30.5%
18/59
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/137
|
5.1%
7/137
|
3.5%
5/141
|
5.4%
3/56
|
3.4%
2/59
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.9%
15/137
|
8.8%
12/137
|
9.9%
14/141
|
16.1%
9/56
|
11.9%
7/59
|
|
Gastrointestinal disorders
Constipation
|
34.3%
47/137
|
35.0%
48/137
|
25.5%
36/141
|
50.0%
28/56
|
37.3%
22/59
|
|
Gastrointestinal disorders
Diarrhoea
|
75.2%
103/137
|
78.1%
107/137
|
89.4%
126/141
|
80.4%
45/56
|
78.0%
46/59
|
|
Gastrointestinal disorders
Dyspepsia
|
17.5%
24/137
|
15.3%
21/137
|
14.9%
21/141
|
12.5%
7/56
|
18.6%
11/59
|
|
Gastrointestinal disorders
Flatulence
|
11.7%
16/137
|
10.2%
14/137
|
9.2%
13/141
|
12.5%
7/56
|
3.4%
2/59
|
|
Gastrointestinal disorders
Haemorrhoids
|
6.6%
9/137
|
2.9%
4/137
|
3.5%
5/141
|
10.7%
6/56
|
11.9%
7/59
|
|
Gastrointestinal disorders
Nausea
|
75.9%
104/137
|
67.9%
93/137
|
76.6%
108/141
|
82.1%
46/56
|
62.7%
37/59
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
2.9%
4/137
|
5.8%
8/137
|
5.0%
7/141
|
8.9%
5/56
|
6.8%
4/59
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
2.9%
4/137
|
2.2%
3/137
|
5.7%
8/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Stomatitis
|
38.0%
52/137
|
30.7%
42/137
|
23.4%
33/141
|
48.2%
27/56
|
20.3%
12/59
|
|
Gastrointestinal disorders
Vomiting
|
43.1%
59/137
|
44.5%
61/137
|
59.6%
84/141
|
66.1%
37/56
|
27.1%
16/59
|
|
General disorders
Asthenia
|
13.1%
18/137
|
12.4%
17/137
|
16.3%
23/141
|
10.7%
6/56
|
11.9%
7/59
|
|
General disorders
Chest pain
|
7.3%
10/137
|
2.2%
3/137
|
5.7%
8/141
|
10.7%
6/56
|
6.8%
4/59
|
|
General disorders
Chills
|
8.8%
12/137
|
10.2%
14/137
|
8.5%
12/141
|
14.3%
8/56
|
5.1%
3/59
|
|
General disorders
Fatigue
|
78.1%
107/137
|
69.3%
95/137
|
58.2%
82/141
|
76.8%
43/56
|
62.7%
37/59
|
|
General disorders
Mucosal inflammation
|
13.9%
19/137
|
9.5%
13/137
|
9.9%
14/141
|
21.4%
12/56
|
10.2%
6/59
|
|
General disorders
Oedema
|
5.8%
8/137
|
4.4%
6/137
|
4.3%
6/141
|
0.00%
0/56
|
0.00%
0/59
|
|
General disorders
Oedema peripheral
|
16.8%
23/137
|
13.1%
18/137
|
17.0%
24/141
|
8.9%
5/56
|
3.4%
2/59
|
|
General disorders
Pyrexia
|
21.9%
30/137
|
20.4%
28/137
|
19.9%
28/141
|
21.4%
12/56
|
10.2%
6/59
|
|
Infections and infestations
Herpes simplex
|
5.8%
8/137
|
4.4%
6/137
|
3.5%
5/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Infection
|
2.2%
3/137
|
5.8%
8/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Nasopharyngitis
|
6.6%
9/137
|
5.8%
8/137
|
2.8%
4/141
|
3.6%
2/56
|
5.1%
3/59
|
|
Infections and infestations
Rhinitis
|
3.6%
5/137
|
5.1%
7/137
|
3.5%
5/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Infections and infestations
Upper respiratory tract infection
|
7.3%
10/137
|
6.6%
9/137
|
3.5%
5/141
|
8.9%
5/56
|
5.1%
3/59
|
|
Infections and infestations
Urinary tract infection
|
2.9%
4/137
|
6.6%
9/137
|
4.3%
6/141
|
10.7%
6/56
|
5.1%
3/59
|
|
Investigations
Weight decreased
|
7.3%
10/137
|
8.8%
12/137
|
10.6%
15/141
|
8.9%
5/56
|
6.8%
4/59
|
|
Investigations
Weight increased
|
8.8%
12/137
|
6.6%
9/137
|
3.5%
5/141
|
7.1%
4/56
|
6.8%
4/59
|
|
Metabolism and nutrition disorders
Anorexia
|
29.9%
41/137
|
30.7%
42/137
|
34.0%
48/141
|
39.3%
22/56
|
28.8%
17/59
|
|
Metabolism and nutrition disorders
Dehydration
|
17.5%
24/137
|
13.1%
18/137
|
29.8%
42/141
|
16.1%
9/56
|
13.6%
8/59
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
13.9%
19/137
|
7.3%
10/137
|
8.5%
12/141
|
17.9%
10/56
|
20.3%
12/59
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.5%
13/137
|
5.8%
8/137
|
13.5%
19/141
|
19.6%
11/56
|
8.5%
5/59
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.5%
2/137
|
5.8%
8/137
|
4.3%
6/141
|
5.4%
3/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.6%
20/137
|
11.7%
16/137
|
9.2%
13/141
|
7.1%
4/56
|
8.5%
5/59
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.1%
18/137
|
9.5%
13/137
|
7.8%
11/141
|
23.2%
13/56
|
10.2%
6/59
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
6.6%
9/137
|
2.2%
3/137
|
0.71%
1/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.8%
8/137
|
2.2%
3/137
|
2.8%
4/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
2.2%
3/137
|
5.8%
8/137
|
2.8%
4/141
|
0.00%
0/56
|
5.1%
3/59
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.6%
9/137
|
2.2%
3/137
|
2.1%
3/141
|
12.5%
7/56
|
5.1%
3/59
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.0%
11/137
|
5.1%
7/137
|
4.3%
6/141
|
5.4%
3/56
|
11.9%
7/59
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.9%
15/137
|
8.8%
12/137
|
9.2%
13/141
|
12.5%
7/56
|
5.1%
3/59
|
|
Nervous system disorders
Dizziness
|
19.0%
26/137
|
13.9%
19/137
|
8.5%
12/141
|
30.4%
17/56
|
6.8%
4/59
|
|
Nervous system disorders
Dysgeusia
|
16.1%
22/137
|
14.6%
20/137
|
14.2%
20/141
|
17.9%
10/56
|
5.1%
3/59
|
|
Nervous system disorders
Headache
|
19.7%
27/137
|
17.5%
24/137
|
9.9%
14/141
|
30.4%
17/56
|
15.3%
9/59
|
|
Nervous system disorders
Hypoaesthesia
|
5.1%
7/137
|
2.2%
3/137
|
1.4%
2/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
6.6%
9/137
|
3.6%
5/137
|
3.5%
5/141
|
8.9%
5/56
|
5.1%
3/59
|
|
Nervous system disorders
Syncope
|
5.1%
7/137
|
2.2%
3/137
|
2.8%
4/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Psychiatric disorders
Anxiety
|
10.9%
15/137
|
4.4%
6/137
|
7.1%
10/141
|
12.5%
7/56
|
10.2%
6/59
|
|
Psychiatric disorders
Confusional state
|
3.6%
5/137
|
3.6%
5/137
|
5.0%
7/141
|
5.4%
3/56
|
1.7%
1/59
|
|
Psychiatric disorders
Depression
|
11.7%
16/137
|
10.2%
14/137
|
11.3%
16/141
|
14.3%
8/56
|
10.2%
6/59
|
|
Psychiatric disorders
Insomnia
|
23.4%
32/137
|
22.6%
31/137
|
13.5%
19/141
|
26.8%
15/56
|
23.7%
14/59
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.6%
20/137
|
10.9%
15/137
|
10.6%
15/141
|
33.9%
19/56
|
11.9%
7/59
|
|
Vascular disorders
Hypotension
|
5.8%
8/137
|
4.4%
6/137
|
5.0%
7/141
|
0.00%
0/56
|
0.00%
0/59
|
|
Cardiac disorders
Palpitations
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
10.7%
6/56
|
0.00%
0/59
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
8.9%
5/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
12.5%
7/56
|
5.1%
3/59
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
10.2%
6/59
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
1.7%
1/59
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
8.5%
5/59
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
5.1%
3/59
|
|
General disorders
Chest discomfort
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
0.00%
0/59
|
|
General disorders
Malaise
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
7.1%
4/56
|
0.00%
0/59
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
1.7%
1/59
|
|
General disorders
Pain
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
3.4%
2/59
|
|
Infections and infestations
Catheter site infection
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
0.00%
0/59
|
|
Infections and infestations
Sinusitis
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
7.1%
4/56
|
3.4%
2/59
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Procedural site reaction
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
3.4%
2/59
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
3.6%
2/56
|
5.1%
3/59
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
10.2%
6/59
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
1.7%
1/59
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
10.7%
6/56
|
3.4%
2/59
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
3.6%
2/56
|
5.1%
3/59
|
|
Renal and urinary disorders
Urine abnormality
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
12.5%
7/56
|
3.4%
2/59
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
3.4%
2/59
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
7.1%
4/56
|
5.1%
3/59
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
6.8%
4/59
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
1.7%
1/59
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
3.4%
2/59
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
5.4%
3/56
|
0.00%
0/59
|
|
Surgical and medical procedures
Sinus operation
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
5.1%
3/59
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
1.8%
1/56
|
5.1%
3/59
|
|
Vascular disorders
Thrombosis
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/141
|
7.1%
4/56
|
0.00%
0/59
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER