Comparison of oral amoxicillin and intravenous benzylpenicillin for

Report
PIVOT: IV vs Oral antibiotics for
Pneumonia
Journal Club April 2012
Chris Edwards
Introduction
• What is your clinical practise with moderate to severe
pneumonia?
• “48 hours IVs and then home on orals if culture
negative.”
• But this doesn’t make sense ….
Plan
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PICO
Search
Result
Trial Analysis
Summary
Discussion
PICO
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P- children with pneumonia
I – Oral antibiotics
C – IV antibiotics
O- time to recovery/time in hospital
Search
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Medline
“pneumonia AND antibiotics”
RCTs
Children (0-18 years)
English language
~80 hits
Then looked for developed world(few) rather than
developing world (lots)
Result
• Comparison of oral amoxicillin and intravenous
benzylpenicillin for community acquired pneumonia in
children(PIVOT trial): a multicentre pragmatic
randomised controlled equivalence trial
• M Atkinson, M Lakhanpaul, A Smyth, H Vyas, V Weston,
J Sithole, V Owen, K Halliday, H Sammons, J Crane, N
Guntupalli, L Walton, T Ninan, A Morjaria, T Stephenson
• Thorax 2007;62:1102–1106. doi: 10.1136/thx.2006.074906
Analysis
Analysis
“A study was undertaken to ascertain whether therapeutic equivalence
exists for treatment of community acquired pneumonia by the oral and
IV route.”
 Population: Children, but no upper age limit was specified.
 Intervention: IV v Oral antibiotics
 Outcomes: “therapeutic equivalence” taken as:
 Primary outcome measure was time from randomisation until the
temperature was <38°C for 24 continuous hours and oxygen requirement
had ceased
 Secondary outcomes:
 included time in hospital,
 complications (empyema, readmission, further courses of antibiotics),
 duration of oxygen requirement
 time to resolution of illness.
Analysis
Yes
“A block randomisation sequence stratified by centre was produced using a
random number generator. The sequence was accessed via the internet,
therefore allowing concealment of allocation.
Children were randomly assigned to oral amoxicillin (chosen in preference to
oral penicillin owing to the superior absorption and palatability) or IV benzyl
penicillin.”
So not double blind.
Analysis
• Yes….
Analysis
Analysis
• No.
• Could have cannulated all, given placebo IV to the oral
group and oral placebo to the IV group…
Analysis
• Yes
Analysis
Analysis
Children in the IV group were changed to oral amoxicillin on discharge or sooner
if the clinical team considered their improvement warranted this.
Both groups completed a 1-week course of antibiotics in total.
IV group more likely to require another antibiotic / rescue medication.
?Does this mean there was an inherent difference in the two groups?
Analysis
Analysis
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Time to temperature less than 38.5
Length of time in oxygen
Time to discharge
Time to resolution of symptoms
Number of complications
Analysis
Analysis
Analysis
 Time in hospital and oxygen requirement
 “The median length of hospital stay was significantly shorter in the
oral group than in the IV group (1.77 days (25th–75th centile 1.2–
2.0) and 2.1 days (25th–75th centile 1.8–2.9),respectively, p,0.001).
We also calculated the median of the differences and this was found
to be 0.60 days (0.15–1.13) (IV– oral). “
 Oxygen
 During admission, 18/103 children (17.5%) in the IV group and
28/100 children (28%) in the oral group required oxygen (p=0.07).
The duration of oxygen requirement was significantly longer in the IV
group than in the oral group (median 20.5 vs 11.0 hours, p=0.04).
 Children randomised to IV treatment received a median of 6
doses (25th–75th centile 4.7–7.5) of IV benzyl penicillin before
conversion to oral amoxicillin.
Analysis
• For the primary outcome measure, all p values are for
equivalence. Therefore, a p value of ,0.05 indicates that
the null hypothesis (a difference of .20% exists between
the two treatments) has been disproved.
Analysis
• Yes – Nottingham isn’t that far away (especially now
they widened the M1).
Analysis
• ? Chest X-ray resolution?
• ?Longer follow up?
• ?Lung function?
 Probably wouldn’t make a difference to the decision re:
treatment.
Analysis
• The change in practise maybe to start oral amoxicillin in
AAU and keep overnight. If remains well, then home,
vs
• IV for 48 hours then home. So the benefit probably does
outweigh the costs.
Summary
• Oral antibiotics appear to be equivalent to IV antibiotics
for pneumonia
• Pts on IV antibiotics appear to have more complications
Discussion
• Would you encourage the team to change practice in
AAU?

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