Intravenous or oral antibiotic treatment in adults and children with cystic fibrosis and Pseudomonas aeruginosa infection : the TORPEDO-CF RCT
BACKGROUND: People with cystic fibrosis are susceptible to pulmonary infection with Pseudomonas aeruginosa. This may become chronic and lead to increased mortality and morbidity. If treatment is commenced promptly, infection may be eradicated through prolonged antibiotic treatment.
OBJECTIVE: To compare the clinical effectiveness, cost-effectiveness and safety of two eradication regimens.
DESIGN: This was a Phase IV, multicentre, parallel-group, randomised controlled trial.
SETTING: Seventy UK and two Italian cystic fibrosis centres.
PARTICIPANTS: Participants were individuals with cystic fibrosis aged > 28 days old who had never had a P. aeruginosa infection or who had been infection free for 1 year.
INTERVENTIONS: Fourteen days of intravenous ceftazidime and tobramycin or 3 months of oral ciprofloxacin. Inhaled colistimethate sodium was included in both regimens over 3 months. Consenting patients were randomly allocated to either treatment arm in a 1 : 1 ratio using simple block randomisation with random variable block length.
MAIN OUTCOME MEASURES: The primary outcome was eradication of P. aeruginosa at 3 months and remaining free of infection to 15 months. Secondary outcomes included time to reoccurrence, spirometry, anthropometrics, pulmonary exacerbations and hospitalisations. Primary analysis used intention to treat (powered for superiority). Safety analysis included patients who had received at least one dose of any of the study drugs. Cost-effectiveness analysis explored the cost per successful eradication and the cost per quality-adjusted life-year.
RESULTS: Between 5 October 2010 and 27 January 2017, 286 patients were randomised: 137 patients to intravenous antibiotics and 149 patients to oral antibiotics. The numbers of participants achieving the primary outcome were 55 out of 125 (44%) in the intravenous group and 68 out of 130 (52%) in the oral group. Participants randomised to the intravenous group were less likely to achieve the primary outcome; although the difference between groups was not statistically significant, the clinically important difference that the trial aimed to detect was not contained within the confidence interval (relative risk 0.84, 95% confidence interval 0.65 to 1.09; p = 0.184). Significantly fewer patients in the intravenous group (40/129, 31%) than in the oral group (61/136, 44.9%) were hospitalised in the 12 months following eradication treatment (relative risk 0.69, 95% confidence interval 0.5 to 0.95; p = 0.02). There were no clinically important differences in other secondary outcomes. There were 32 serious adverse events in 24 participants [intravenous: 10/126 (7.9%); oral: 14/146 (9.6%)]. Oral therapy led to reductions in costs compared with intravenous therapy (-£5938.50, 95% confidence interval -£7190.30 to -£4686.70). Intravenous therapy usually necessitated hospital admission, which accounted for a large part of this cost.
LIMITATIONS: Only 15 out of the 286 participants recruited were adults - partly because of the smaller number of adult centres participating in the trial. The possibility that the trial participants may be different from the rest of the cystic fibrosis population and may have had a better clinical status, and so be more likely to agree to the uncertainty of trial participation, cannot be ruled out.
CONCLUSIONS: Intravenous antibiotics did not achieve sustained eradication of P. aeruginosa in a greater proportion of cystic fibrosis patients. Although there were fewer hospitalisations in the intravenous group during follow-up, this confers no advantage over the oral therapy group, as intravenous eradication frequently requires hospitalisation. These results do not support the use of intravenous antibiotics to eradicate P. aeruginosa in cystic fibrosis.
FUTURE WORK: Future research studies should combine long-term follow-up with regimens to reduce reoccurrence after eradication.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN02734162 and EudraCT 2009-012575-10.
FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 65. See the NIHR Journals Library website for further project information.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
|---|---|
| Enthalten in: |
Health technology assessment (Winchester, England) - 25(2021), 65 vom: 22. Nov., Seite 1-128 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Langton Hewer, Simon C [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 30.11.2021 Date Revised 30.11.2021 published: Print ISRCTN: ISRCTN02734162 EudraCT: 2009-012575-10 Citation Status MEDLINE |
|---|
| doi: |
10.3310/hta25650 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM333443098 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM333443098 | ||
| 003 | DE-627 | ||
| 005 | 20231225221651.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3310/hta25650 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1111.xml |
| 035 | |a (DE-627)NLM333443098 | ||
| 035 | |a (NLM)34806975 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Langton Hewer, Simon C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intravenous or oral antibiotic treatment in adults and children with cystic fibrosis and Pseudomonas aeruginosa infection |b the TORPEDO-CF RCT |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 30.11.2021 | ||
| 500 | |a Date Revised 30.11.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a ISRCTN: ISRCTN02734162 | ||
| 500 | |a EudraCT: 2009-012575-10 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: People with cystic fibrosis are susceptible to pulmonary infection with Pseudomonas aeruginosa. This may become chronic and lead to increased mortality and morbidity. If treatment is commenced promptly, infection may be eradicated through prolonged antibiotic treatment | ||
| 520 | |a OBJECTIVE: To compare the clinical effectiveness, cost-effectiveness and safety of two eradication regimens | ||
| 520 | |a DESIGN: This was a Phase IV, multicentre, parallel-group, randomised controlled trial | ||
| 520 | |a SETTING: Seventy UK and two Italian cystic fibrosis centres | ||
| 520 | |a PARTICIPANTS: Participants were individuals with cystic fibrosis aged > 28 days old who had never had a P. aeruginosa infection or who had been infection free for 1 year | ||
| 520 | |a INTERVENTIONS: Fourteen days of intravenous ceftazidime and tobramycin or 3 months of oral ciprofloxacin. Inhaled colistimethate sodium was included in both regimens over 3 months. Consenting patients were randomly allocated to either treatment arm in a 1 : 1 ratio using simple block randomisation with random variable block length | ||
| 520 | |a MAIN OUTCOME MEASURES: The primary outcome was eradication of P. aeruginosa at 3 months and remaining free of infection to 15 months. Secondary outcomes included time to reoccurrence, spirometry, anthropometrics, pulmonary exacerbations and hospitalisations. Primary analysis used intention to treat (powered for superiority). Safety analysis included patients who had received at least one dose of any of the study drugs. Cost-effectiveness analysis explored the cost per successful eradication and the cost per quality-adjusted life-year | ||
| 520 | |a RESULTS: Between 5 October 2010 and 27 January 2017, 286 patients were randomised: 137 patients to intravenous antibiotics and 149 patients to oral antibiotics. The numbers of participants achieving the primary outcome were 55 out of 125 (44%) in the intravenous group and 68 out of 130 (52%) in the oral group. Participants randomised to the intravenous group were less likely to achieve the primary outcome; although the difference between groups was not statistically significant, the clinically important difference that the trial aimed to detect was not contained within the confidence interval (relative risk 0.84, 95% confidence interval 0.65 to 1.09; p = 0.184). Significantly fewer patients in the intravenous group (40/129, 31%) than in the oral group (61/136, 44.9%) were hospitalised in the 12 months following eradication treatment (relative risk 0.69, 95% confidence interval 0.5 to 0.95; p = 0.02). There were no clinically important differences in other secondary outcomes. There were 32 serious adverse events in 24 participants [intravenous: 10/126 (7.9%); oral: 14/146 (9.6%)]. Oral therapy led to reductions in costs compared with intravenous therapy (-£5938.50, 95% confidence interval -£7190.30 to -£4686.70). Intravenous therapy usually necessitated hospital admission, which accounted for a large part of this cost | ||
| 520 | |a LIMITATIONS: Only 15 out of the 286 participants recruited were adults - partly because of the smaller number of adult centres participating in the trial. The possibility that the trial participants may be different from the rest of the cystic fibrosis population and may have had a better clinical status, and so be more likely to agree to the uncertainty of trial participation, cannot be ruled out | ||
| 520 | |a CONCLUSIONS: Intravenous antibiotics did not achieve sustained eradication of P. aeruginosa in a greater proportion of cystic fibrosis patients. Although there were fewer hospitalisations in the intravenous group during follow-up, this confers no advantage over the oral therapy group, as intravenous eradication frequently requires hospitalisation. These results do not support the use of intravenous antibiotics to eradicate P. aeruginosa in cystic fibrosis | ||
| 520 | |a FUTURE WORK: Future research studies should combine long-term follow-up with regimens to reduce reoccurrence after eradication | ||
| 520 | |a TRIAL REGISTRATION: Current Controlled Trials ISRCTN02734162 and EudraCT 2009-012575-10 | ||
| 520 | |a FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 65. See the NIHR Journals Library website for further project information | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CYSTIC FIBROSIS | |
| 650 | 4 | |a ERADICATION | |
| 650 | 4 | |a INTRAVENOUS THERAPY | |
| 650 | 4 | |a ORAL THERAPY | |
| 650 | 4 | |a PSEUDOMONAS AERUGINOSA | |
| 650 | 4 | |a RANDOMISED CONTROLLED TRIAL | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Tobramycin |2 NLM | |
| 650 | 7 | |a VZ8RRZ51VK |2 NLM | |
| 700 | 1 | |a Smyth, Alan R |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Michaela |e verfasserin |4 aut | |
| 700 | 1 | |a Jones, Ashley P |e verfasserin |4 aut | |
| 700 | 1 | |a Hickey, Helen |e verfasserin |4 aut | |
| 700 | 1 | |a Kenna, Dervla |e verfasserin |4 aut | |
| 700 | 1 | |a Ashby, Deborah |e verfasserin |4 aut | |
| 700 | 1 | |a Thompson, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Sutton, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Clayton, Dannii |e verfasserin |4 aut | |
| 700 | 1 | |a Arch, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Tanajewski, Łukasz |e verfasserin |4 aut | |
| 700 | 1 | |a Berdunov, Vladislav |e verfasserin |4 aut | |
| 700 | 1 | |a Williamson, Paula R |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Health technology assessment (Winchester, England) |d 1998 |g 25(2021), 65 vom: 22. Nov., Seite 1-128 |w (DE-627)NLM093582129 |x 2046-4924 |7 nnns |
| 773 | 1 | 8 | |g volume:25 |g year:2021 |g number:65 |g day:22 |g month:11 |g pages:1-128 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3310/hta25650 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 25 |j 2021 |e 65 |b 22 |c 11 |h 1-128 | ||