Trial Outcomes & Findings for Early Methicillin-resistant Staphylococcus Aureus (MRSA) Therapy in Cystic Fibrosis (CF) (NCT NCT01349192)
NCT ID: NCT01349192
Last Updated: 2017-05-15
Results Overview
Proportion of subjects with a negative culture for MRSA at Day 28.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
47 participants
Primary outcome timeframe
Day 28
Results posted on
2017-05-15
Participant Flow
The trial was conducted from April 1, 2011 to September 2014 at 14 CF Foundation accredited care centers in the United States.
Participant milestones
| Measure |
Treatment
Oral antibiotics:
1. Rifampin: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.
2. Trimethoprim/Sulfamethoxazole: Adult Dose: 320/1600 orally twice daily for 14 days.
Pediatric Dose: \<40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Alternative 2) Minocycline: subjects greater or equal to 8 years unable to take TMP/SMX or whose screening MRSA is resistant to TMP/SMX are prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: \< 50 kg : 2mg/kg orally twice daily for 14 days max 200mg per day.
Topical:
Mupirocin: 1 gram 2% nasal ointment twice daily for 14 days.
Topical: 0.12% chlorhexidine gluconate oral rinse: for 14 days.
Environmental disinfection of high use areas
|
Observational
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
23
|
|
Overall Study
Evaluable for Primary Endpoint
|
22
|
19
|
|
Overall Study
Withdrawals
|
3
|
6
|
|
Overall Study
COMPLETED
|
21
|
17
|
|
Overall Study
NOT COMPLETED
|
3
|
6
|
Reasons for withdrawal
| Measure |
Treatment
Oral antibiotics:
1. Rifampin: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.
2. Trimethoprim/Sulfamethoxazole: Adult Dose: 320/1600 orally twice daily for 14 days.
Pediatric Dose: \<40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Alternative 2) Minocycline: subjects greater or equal to 8 years unable to take TMP/SMX or whose screening MRSA is resistant to TMP/SMX are prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: \< 50 kg : 2mg/kg orally twice daily for 14 days max 200mg per day.
Topical:
Mupirocin: 1 gram 2% nasal ointment twice daily for 14 days.
Topical: 0.12% chlorhexidine gluconate oral rinse: for 14 days.
Environmental disinfection of high use areas
|
Observational
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.
|
|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
|
Overall Study
Failure to adhere to Protocol
|
2
|
0
|
Baseline Characteristics
Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
Baseline characteristics by cohort
| Measure |
Treatment
n=24 Participants
Oral antibiotics:
1. Rifampin: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.
2. Trimethoprim/Sulfamethoxazole: Adult Dose: 320/1600 orally twice daily for 14 days.
Pediatric Dose: \<40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Alternative 2) Minocycline: subjects greater or equal to 8 years unable to take TMP/SMX or whose screening MRSA is resistant to TMP/SMX are prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: \< 50 kg : 2mg/kg orally twice daily for 14 days max 200mg per day.
Topical:
Mupirocin: 1 gram 2% nasal ointment twice daily for 14 days.
Topical: 0.12% chlorhexidine gluconate oral rinse: for 14 days.
Environmental disinfection of high use areas
|
Observational
n=21 Participants
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
12.3 years
STANDARD_DEVIATION 6.6 • n=24 Participants
|
10.5 years
STANDARD_DEVIATION 5.5 • n=21 Participants
|
11.5 years
STANDARD_DEVIATION 6.1 • n=45 Participants
|
|
Age, Customized
Age Category · >=4 and <12 years
|
13 Participants
n=24 Participants
|
15 Participants
n=21 Participants
|
28 Participants
n=45 Participants
|
|
Age, Customized
Age Category · >=12 and <18 years
|
6 Participants
n=24 Participants
|
5 Participants
n=21 Participants
|
11 Participants
n=45 Participants
|
|
Age, Customized
Age Category · >18 years
|
5 Participants
n=24 Participants
|
1 Participants
n=21 Participants
|
6 Participants
n=45 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=24 Participants
|
10 Participants
n=21 Participants
|
20 Participants
n=45 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=24 Participants
|
11 Participants
n=21 Participants
|
25 Participants
n=45 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity Combined · Caucasian
|
19 Participants
n=24 Participants
|
17 Participants
n=21 Participants
|
36 Participants
n=45 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity Combined · Hispanic
|
3 Participants
n=24 Participants
|
2 Participants
n=21 Participants
|
5 Participants
n=45 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity Combined · African-American
|
1 Participants
n=24 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=45 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity Combined · Other
|
1 Participants
n=24 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=45 Participants
|
|
CF Genotype
Delta F508 Homozygous
|
6 Participants
n=24 Participants
|
12 Participants
n=21 Participants
|
18 Participants
n=45 Participants
|
|
CF Genotype
Delta F508 Heterozygous
|
14 Participants
n=24 Participants
|
7 Participants
n=21 Participants
|
21 Participants
n=45 Participants
|
|
CF Genotype
Other
|
4 Participants
n=24 Participants
|
2 Participants
n=21 Participants
|
6 Participants
n=45 Participants
|
|
CF Genotype
Unidentified
|
0 Participants
n=24 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=45 Participants
|
|
FEV1 Percent of Predicted
|
98.5 percent
STANDARD_DEVIATION 21.6 • n=20 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
101.2 percent
STANDARD_DEVIATION 11.8 • n=17 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
99.8 percent
STANDARD_DEVIATION 17.6 • n=37 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
|
FEV1 Percent of Predicted Category
>=30% to <=50%
|
1 Participants
n=20 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
0 Participants
n=17 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
1 Participants
n=37 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
|
FEV1 Percent of Predicted Category
>50% to <=75%
|
1 Participants
n=20 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
0 Participants
n=17 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
1 Participants
n=37 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
|
FEV1 Percent of Predicted Category
>75% to <=100%
|
7 Participants
n=20 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
5 Participants
n=17 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
12 Participants
n=37 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
|
FEV1 Percent of Predicted Category
>100%
|
11 Participants
n=20 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
12 Participants
n=17 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
23 Participants
n=37 Participants • Lung function was assessed for the subset of participants that were ≥ 6 years old and able to reliably perform spirometry.
|
PRIMARY outcome
Timeframe: Day 28Population: The analysis population is defined as all of the participants who were randomized to a study arm and were assessed for the primary microbiologic efficacy endpoint at both baseline and Day 28.
Proportion of subjects with a negative culture for MRSA at Day 28.
Outcome measures
| Measure |
Treatment
n=22 Participants
Oral antibiotics:
Rifampin: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.
Trimethoprim/Sulfamethoxazole: Adult Dose: 320/1600 orally twice daily for 14 days.
Pediatric Dose: \<40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Alternative 2) Minocycline: subjects greater or equal to 8 years unable to take TMP/SMX or whose screening MRSA is resistant to TMP/SMX are prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: \< 50 kg : 2mg/kg orally twice daily for 14 days max 200mg per day.
Topical:
Mupirocin: 1 gram 2% nasal ointment twice daily for 14 days. Topical: 0.12% chlorhexidine gluconate oral rinse: for 14 days. Environmental disinfection of high use areas
|
Observation
n=19 Participants
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.
|
|---|---|---|
|
MRSA Culture Status
|
18 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Intention to treat
Proportion of subjects treated with oral, inhaled, and IV antibiotics over the 6 month study.
Outcome measures
| Measure |
Treatment
n=24 Participants
Oral antibiotics:
Rifampin: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.
Trimethoprim/Sulfamethoxazole: Adult Dose: 320/1600 orally twice daily for 14 days.
Pediatric Dose: \<40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Alternative 2) Minocycline: subjects greater or equal to 8 years unable to take TMP/SMX or whose screening MRSA is resistant to TMP/SMX are prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: \< 50 kg : 2mg/kg orally twice daily for 14 days max 200mg per day.
Topical:
Mupirocin: 1 gram 2% nasal ointment twice daily for 14 days. Topical: 0.12% chlorhexidine gluconate oral rinse: for 14 days. Environmental disinfection of high use areas
|
Observation
n=21 Participants
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.
|
|---|---|---|
|
Antibiotic Use (Proportion of Subjects)
|
17 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Intention to treat
Days of use of oral, inhaled, and IV antibiotics over the 6 month study.
Outcome measures
| Measure |
Treatment
n=24 Participants
Oral antibiotics:
Rifampin: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.
Trimethoprim/Sulfamethoxazole: Adult Dose: 320/1600 orally twice daily for 14 days.
Pediatric Dose: \<40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Alternative 2) Minocycline: subjects greater or equal to 8 years unable to take TMP/SMX or whose screening MRSA is resistant to TMP/SMX are prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: \< 50 kg : 2mg/kg orally twice daily for 14 days max 200mg per day.
Topical:
Mupirocin: 1 gram 2% nasal ointment twice daily for 14 days. Topical: 0.12% chlorhexidine gluconate oral rinse: for 14 days. Environmental disinfection of high use areas
|
Observation
n=21 Participants
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.
|
|---|---|---|
|
Antibiotic Use (Days of Use Per Subject)
|
21.9 days
Standard Deviation 23.7
|
31.3 days
Standard Deviation 44.0
|
SECONDARY outcome
Timeframe: 28 daysPopulation: Intention to treat
Proportion of subjects with a protocol-defined pulmonary exacerbation (PE) between baseline and day 28 who are treated with antibiotics active against MRSA.
Outcome measures
| Measure |
Treatment
n=24 Participants
Oral antibiotics:
Rifampin: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.
Trimethoprim/Sulfamethoxazole: Adult Dose: 320/1600 orally twice daily for 14 days.
Pediatric Dose: \<40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Alternative 2) Minocycline: subjects greater or equal to 8 years unable to take TMP/SMX or whose screening MRSA is resistant to TMP/SMX are prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: \< 50 kg : 2mg/kg orally twice daily for 14 days max 200mg per day.
Topical:
Mupirocin: 1 gram 2% nasal ointment twice daily for 14 days. Topical: 0.12% chlorhexidine gluconate oral rinse: for 14 days. Environmental disinfection of high use areas
|
Observation
n=21 Participants
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.
|
|---|---|---|
|
Pulmonary Exacerbations
|
2 Participants
|
6 Participants
|
Adverse Events
Treatment
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Observation
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment
n=24 participants at risk
Oral antibiotics:
Rifampin: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.
Trimethoprim/Sulfamethoxazole: Adult Dose: 320/1600 orally twice daily for 14 days.
Pediatric Dose: \<40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Alternative 2) Minocycline: subjects greater or equal to 8 years unable to take TMP/SMX or whose screening MRSA is resistant to TMP/SMX are prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: \< 50 kg : 2mg/kg orally twice daily for 14 days max 200mg per day.
Topical:
Mupirocin: 1 gram 2% nasal ointment twice daily for 14 days. Topical: 0.12% chlorhexidine gluconate oral rinse: for 14 days. Environmental disinfection of high use areas
|
Observation
n=21 participants at risk
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.
|
|---|---|---|
|
Infections and infestations
Cellulitis
|
4.2%
1/24 • Number of events 1 • 28 days
|
0.00%
0/21 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/24 • 28 days
|
4.8%
1/21 • Number of events 1 • 28 days
|
Other adverse events
| Measure |
Treatment
n=24 participants at risk
Oral antibiotics:
Rifampin: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.
Trimethoprim/Sulfamethoxazole: Adult Dose: 320/1600 orally twice daily for 14 days.
Pediatric Dose: \<40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Alternative 2) Minocycline: subjects greater or equal to 8 years unable to take TMP/SMX or whose screening MRSA is resistant to TMP/SMX are prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: \< 50 kg : 2mg/kg orally twice daily for 14 days max 200mg per day.
Topical:
Mupirocin: 1 gram 2% nasal ointment twice daily for 14 days. Topical: 0.12% chlorhexidine gluconate oral rinse: for 14 days. Environmental disinfection of high use areas
|
Observation
n=21 participants at risk
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
4/24 • Number of events 4 • 28 days
|
0.00%
0/21 • 28 days
|
|
Gastrointestinal disorders
Nausea
|
25.0%
6/24 • Number of events 7 • 28 days
|
9.5%
2/21 • Number of events 2 • 28 days
|
|
Gastrointestinal disorders
Vomiting
|
20.8%
5/24 • Number of events 8 • 28 days
|
4.8%
1/21 • Number of events 1 • 28 days
|
|
General disorders
Pyrexia
|
12.5%
3/24 • Number of events 3 • 28 days
|
4.8%
1/21 • Number of events 3 • 28 days
|
|
Investigations
Weight decreased
|
0.00%
0/24 • 28 days
|
9.5%
2/21 • Number of events 2 • 28 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.2%
1/24 • Number of events 1 • 28 days
|
9.5%
2/21 • Number of events 2 • 28 days
|
|
Nervous system disorders
Headache
|
8.3%
2/24 • Number of events 2 • 28 days
|
0.00%
0/21 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
41.7%
10/24 • Number of events 10 • 28 days
|
42.9%
9/21 • Number of events 10 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.3%
2/24 • Number of events 3 • 28 days
|
4.8%
1/21 • Number of events 1 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.5%
3/24 • Number of events 3 • 28 days
|
4.8%
1/21 • Number of events 1 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
4.2%
1/24 • Number of events 1 • 28 days
|
14.3%
3/21 • Number of events 3 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
8.3%
2/24 • Number of events 2 • 28 days
|
4.8%
1/21 • Number of events 1 • 28 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.5%
3/24 • Number of events 3 • 28 days
|
0.00%
0/21 • 28 days
|
Additional Information
Marianne S. Muhlebach, PI
University of North Carolina, Chapel Hill
Phone: (1) 919 966 1055
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place