Trial Outcomes & Findings for A Study To Evaluate The Effects Of Celecoxib (Celebrex®) Or Naproxen On Blood Pressure In Pediatric Subjects (NCT NCT00807846)

NCT ID: NCT00807846

Last Updated: 2021-02-02

Results Overview

Value at 6 weeks minus value at baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 201 participants
• Primary outcome timeframe: 6 Weeks/Final Visit
• Results posted on: 2021-02-02

Participant Flow

This was a phase 4, 6-week, randomized double-blind, multicenter, active-controlled trial in participants with juvenile idiopathic arthritis (JIA). A total of 221 participants were screened into the study in 32 investigator sites.

A total of 101 participants were randomized to treatment with Celecoxib and 100 participants to treatment with Naproxen. Of these randomized, 100 participants received treatment with Celecoxib and 98 participants received treatment with Naproxen. Three participants were randomized but did not receive any treatment.

Participant milestones

Measure	Celecoxib Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Overall Study STARTED	100	98
Overall Study COMPLETED	88	94
Overall Study NOT COMPLETED	12	4

Reasons for withdrawal

Measure	Celecoxib Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Overall Study Adverse Event	5	0
Overall Study Lack of Efficacy	2	0
Overall Study Protocol Violation	2	1
Overall Study Withdrawal by Subject	2	1
Overall Study Other	1	2

Baseline Characteristics

A Study To Evaluate The Effects Of Celecoxib (Celebrex®) Or Naproxen On Blood Pressure In Pediatric Subjects

Baseline characteristics by cohort

Measure	Celecoxib n=100 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Total n=198 Participants Total of all reporting groups
Age, Customized >=2 - <8 Years	22 Participants n=5 Participants	18 Participants n=7 Participants	40 Participants n=5 Participants
Age, Customized >=8 - <13 Years	34 Participants n=5 Participants	47 Participants n=7 Participants	81 Participants n=5 Participants
Age, Customized >=13 - <18 Years	44 Participants n=5 Participants	33 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	64 Participants n=7 Participants	140 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	34 Participants n=7 Participants	58 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 Weeks/Final Visit

Population: Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP (blood pressure) measurements. For early terminations the last observation carried forward (LOCF) was used to impute missing data.

Value at 6 weeks minus value at baseline.

Outcome measures

Measure	Celecoxib n=100 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in Systolic Blood Pressure (SBP) at Week 6/Final Visit	0.366 mmHg (millimeter of mercury) Standard Error 0.70	-0.734 mmHg (millimeter of mercury) Standard Error 0.70

SECONDARY outcome

Timeframe: 2 weeks

Population: Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Value at 2 weeks minus value at baseline.

Outcome measures

Measure	Celecoxib n=100 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline to Week 2 in SBP.	-0.202 mmHg Standard Error 0.53	-1.290 mmHg Standard Error 0.53

SECONDARY outcome

Timeframe: 4 weeks

Population: Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Value at 4 weeks minus value at baseline.

Outcome measures

Measure	Celecoxib n=100 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in SBP at Week 4.	-0.170 mmHg Standard Error 0.58	-2.007 mmHg Standard Error 0.58

SECONDARY outcome

Timeframe: 2 weeks

Population: Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Value at 2 weeks minus value at baseline.

Outcome measures

Measure	Celecoxib n=100 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in Diastolic Blood Pressure (DBP) at Week 2.	-1.346 mmHg Standard Error 0.52	-0.139 mmHg Standard Error 0.52

SECONDARY outcome

Timeframe: 4 weeks

Population: Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Value at 4 weeks minus value at baseline.

Outcome measures

Measure	Celecoxib n=100 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in DBP at Week 4.	-0.628 mmHg Standard Error 0.54	-0.848 mmHg Standard Error 0.54

SECONDARY outcome

Timeframe: 6 weeks

Population: Safety population included all randomized participants who received at least one dose of study medication. The Safety Analysis set was used to analyze all BP measurements. For early terminations the LOCF was used to impute missing data.

Value at 6 weeks/Final Visit minus value at baseline.

Outcome measures

Measure	Celecoxib n=100 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in DBP at Week 6/Final Visit	-0.535 mmHg Standard Error 0.54	-0.356 mmHg Standard Error 0.54

SECONDARY outcome

Timeframe: 6 weeks

Population: Modified-Intent-to-Treat (MITT) Population included all randomized participants who received at least one dose of study medication and had at least one post-baseline efficacy measurement.

The parent/legal guardian evaluated the participant's overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the visual analog scale (VAS). The VAS ranged from 0 to 100, with 0 being 'very well' and 100 being 'very poor.

Outcome measures

Measure	Celecoxib n=98 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in Parent's Assessment of Overall Well-being at Week 6/Final Visit.	-10.581 mm (millimeter) Standard Error 2.081	-13.614 mm (millimeter) Standard Error 2.060

SECONDARY outcome

Timeframe: Week 6/Final Visit

Population: The MITT Population included all randomized participants who received at least one dose of study medication and had at least one post-baseline efficacy measurement.

The parent/legal guardian evaluated the participant's overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the visual analog scale (VAS). The VAS ranged from 0 to 100, with 0 being 'very well' and 100 being 'very poor.

Outcome measures

Measure	Celecoxib n=98 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Number of Participants With >= 30% Improvement in the Parent's Global Assessment of Overall Well-being at Week 6/Final Visit.	47 Participants	54 Participants

SECONDARY outcome

Timeframe: 6 weeks

Population: MITT population was used. Additional 3 participants aged \<8 yrs at Baseline in Naproxen Arm provided self-assessments. In Celecoxib Arm, 2 participants (\>=8 yrs) not provided self-assessment and 2 (\>=8 yrs) provided but they were not from MITT and were excluded; additional 1 participant (\<8 yrs) provided self-assessment and included in analysis.

Participants, ≥8 years of age at the baseline, evaluated their own overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the VAS. The VAS ranges from 0 to 100, with 0 being 'very well' and 100 being 'very poor'.

Outcome measures

Measure	Celecoxib n=75 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=83 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in Participant's Assessment of Overall Well-being at Week 6/Final Visit.	-12.990 mm Standard Error 2.226	-12.588 mm Standard Error 2.115

SECONDARY outcome

Timeframe: Week 6/Final Visit

Population: MITT population was used. Additional 3 participants aged \<8 yrs at Baseline in Naproxen Arm provided self-assessments. In Celecoxib Arm, 2 participants (\>=8 yrs) not provided self-assessment and 2 (\>=8 yrs) provided but they were not from MITT and were excluded; additional 1 participant (\<8 yrs) provided self-assessment and included in analysis.

Participants, ≥8 years of age at the baseline, evaluated their own overall well-being at Baseline and at Week 6 (or Final Visit) by placing one vertical line on the VAS. The VAS ranges from 0 to 100, with 0 being 'very well' and 100 being 'very poor'.

Outcome measures

Measure	Celecoxib n=75 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=83 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Number of Participants With >= 30% Improvement in the Participant's Global Assessment of Overall Well-being at Week 6/Final Visit.	33 Participants	45 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks/Final Visit

Population: Safety population included all randomized participants who received at least one dose of study medication. For one participant in Naproxen Arm the device failed to collect 11 out of 24 readings at Week 6 and this participant was not included in analysis. ABPM data were analyzed for 12 and 11 participants in Celecoxib and Naproxen Arms respectively.

Ambulatory BP measurements were obtained from 24 participants(in addition to the BP measurements obtained by the cuff technique) participating in the exploratory 24-hour ABPM sub-study. BP was monitored by a 24 hour Ambulatory BP device provided by a central vendor.

Outcome measures

Measure	Celecoxib n=12 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=11 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in Assessment of Ambulatory Blood Pressure Monitoring (ABPM) for SBP and DBP at Week 6/Final Visit SBP	2.4 mmHg Standard Deviation 7.02	-1.7 mmHg Standard Deviation 12.40
Change From Baseline in Assessment of Ambulatory Blood Pressure Monitoring (ABPM) for SBP and DBP at Week 6/Final Visit DBP	0.9 mmHg Standard Deviation 4.23	-1.1 mmHg Standard Deviation 5.36

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks/Final Visit

Population: Safety population included all randomized participants who received at least one dose of study medication. For one participant in Naproxen Arm the device failed to collect 11 out of 24 readings at Week 6 and this participant was not included in analysis. ABPM data were analyzed for 12 and 11 participants in Celecoxib and Naproxen Arms respectively.

Ambulatory BP measurements were obtained from 24 participants (in addition to the BP measurements obtained by the cuff technique) participating in the exploratory 24-hour ABPM sub-study. A summary of ABPM 24-hour averages for heart rate is presented in this Outcome Measure.

Outcome measures

Measure	Celecoxib n=12 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=11 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in Assessment of ABPM for Heart Rate at Week 6/Final Visit	2.5 bpm (beats per minute) Standard Deviation 6.34	3.7 bpm (beats per minute) Standard Deviation 8.50

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks/Final Visit

Population: Safety population included all randomized participants who received at least one dose of study medication. A total of 22 out of 24 participants were analyzed in this sensitivity analysis. Two participants were excluded, one due to outlying BP values at Baseline and another due to the device failure to collect 11 out of 24 readings).

A summary of ABPM 24-hour averages for SBP and DBP are presented in this Outcome Measure. One of the participant in the Naproxen ABPM Arm had clinically implausible high BP values at Baseline. Due to the low number of participants in each Arm (12 and 11) these values had a significant impact on the mean baseline values for the Naproxen Arm. As a result, an additional sensitivity analysis was conducted, excluding this participant (Participant ID 10031002).

Outcome measures

Measure	Celecoxib n=12 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=10 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in Assessment of ABPM for SBP and DBP Pressure at Week 6/Final Visit (Sensitivity Analysis Excluding One Participant) SBP	2.4 mmHg Standard Deviation 7.02	1.9 mmHg Standard Deviation 4.13
Change From Baseline in Assessment of ABPM for SBP and DBP Pressure at Week 6/Final Visit (Sensitivity Analysis Excluding One Participant) DBP	0.9 mmHg Standard Deviation 4.23	0.3 mmHg Standard Deviation 2.86

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks/Final Visit

Population: Safety population included all randomized participants who received at least one dose of study medication. A total of 22 out of 24 participants were analyzed in this sensitivity analysis. Two participants were excluded, one due to outlying BP values at Baseline and another due to the device failure to collect 11 out of 24 readings).

A summary of ABPM 24-hour averages for heart rate is presented in this Outcome Measure. One of the participant in the Naproxen ABPM Arm had clinically implausible high BP values at Baseline. Due to the low number of participants in each Arm (12 and 11) these values had a significant impact on the mean baseline values for the Naproxen Arm. As a result, an additional sensitivity analysis was conducted, excluding this participant (Participant ID 10031002).

Outcome measures

Measure	Celecoxib n=12 Participants Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=10 Participants Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Change From Baseline in Assessment of ABPM for Heart Rate at Week 6/Final Visit (Sensitivity Analysis Excluding One Participant)	2.5 bpm Standard Deviation 6.34	3.3 bpm Standard Deviation 8.82

Adverse Events

Celecoxib

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Naproxen

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Celecoxib n=100 participants at risk Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 participants at risk Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Injury, poisoning and procedural complications Hand fracture	0.00% 0/100 • Up to Week 6/Final Visit The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.0% 1/98 • Up to Week 6/Final Visit The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	Celecoxib n=100 participants at risk Participants received celecoxib capsules 50 mg twice daily (BID) or 100 mg BID for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit	Naproxen n=98 participants at risk Participants received naproxen suspension 7.5 mg/kg BID (maximum dose of 500 mg BID) for 6 weeks. The volume/dose of the study medications was determined by the subject's weight at Baseline visit
Gastrointestinal disorders Nausea	4.0% 4/100 • Up to Week 6/Final Visit The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.2% 9/98 • Up to Week 6/Final Visit The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	1.0% 1/100 • Up to Week 6/Final Visit The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.1% 5/98 • Up to Week 6/Final Visit The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	7.0% 7/100 • Up to Week 6/Final Visit The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.1% 4/98 • Up to Week 6/Final Visit The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER