CORONIS-Background.ppt international study of Cesarean section technique

CORONIS-Background.ppt international study of Cesarean section technique Cesarean section section technique

1. International study of caesarean
section surgical techniques: a
randomised factorial trial

2. Rationale for CORONIS
• Caesarean section common around the world
• By improving surgical techniques, we have potential
to improve the health of very many women
• Many existing trials have drawbacks (small sample
size, poor methodology, less relevant outcomes)

3. UK Caesar Trial
• Trial of 3,000 women, completed in UK (& Italy) in
2007
• Interventions
single vs double layer closure of the uterus
non-closure vs closure of pelvic peritoneum
liberal vs restricted use of a sub-sheath drain

4. WHO sponsored meeting 2002
• Delegates from 9 countries met in Oxford for 5 days
• Discussed and agreed list of interventions to explore
in international trial
• NPEU team drew up draft protocol and draft data
collection instrument leading to MRC application

5. 1. Catheterisation
• routine catheterisation vs no catheterisation
• in-dwelling vs in-and-out catheter
• in-dwelling catheter for duration of CS vs for longer
2. Abdominal entry – sharp vs blunt *
* Chosen for CORONIS trial
Interventions considered for CORONIS:

6. 3. Uterus
a) Sharp vs blunt uterine entry
b) Exteriorisation of uterus for repair vs intra-abdominal repair *
c) Uterine swabbing vs no swabbing prior to uterine closure
d) Single vs double layer uterine closure *
e) Uterine repair:
•chromic catgut vs vicryl (polyglactin-910) *
•locking vs non-locking suture
•continuous vs interrupted sutures
* Chosen for CORONIS trial
Interventions considered for CORONIS:

7. 4. Peritoneum
a) peritoneal closure vs non-closure *
pelvic
parietal
both
b) Materials for closure of the peritoneum
plain catgut vs vicryl (polyglactin-910) vs chromic catgut
5. Sheath
Chromic catgut vs plain catgut vs vicryl (polyglactin-910) for sheath repair
Locked continuous vs non-locked continuous closure
* Chosen for CORONIS trial
Interventions considered for CORONIS:

8. 6. Fat
Subcutaneous fat closure vs no closure
7. Skin closure
Subcutaneous absorbable suture vs interrupted absorbable suture,
staples etc
Interventions considered for CORONIS:

9. Meeting of co-investigators 2006
• Delegates from 6 countries met in Oxford for 3 days
• Reviewed and agreed final list of interventions

10. Systematic reviews - Cochrane
Long-term follow-up studies
Key outcomes:
Febrile morbidity
Wound infection
Endometritis
Blood transfusion
Infant outcomes if intervention occurs prior to delivery
of baby, such as abdominal entry or uterine entry
Review of the interventions considered

11. 1.Abdominal entry – sharp (Pfannenstiel) vs blunt (Joel
Cohen)
Cochrane review
2 RCTs, n=411
Both suggest improvement in febrile morbidity with J-C
There was little difference in wound infection
No data available for endometritis
Review of interventions considered:

12. Joel-Cohen versus Pfannenstiel incision
Outcome: Postoperative febrile morbidity

13. Joel-Cohen versus Pfannenstiel incision
Outcome: Wound infection as defined by trial authors

14. 2.Exteriorisation of uterus for repair vs intra-
abdominal repair
Cochrane review
6 RCTs, n=1294
Exteriorisation associated with reduction in febrile
morbidity but no effect on endometritis, wound
complication, sepsis or blood transfusion
Review of interventions considered:

15. Uterine exteriorization vs intraperitoneal repair at CS
Outcome: Febrile morbidity for more than 3 days
 

16. Uterine exteriorization vs intraperitoneal repair at CS
Outcome: Endometritis
 

17. Uterine exteriorization vs intraperitoneal repair at CS
Outcome: Wound complications (infection, haematoma,
breakdown)
 

18. Uterine exteriorization vs intraperitoneal repair at CS
Outcome: Postoperative sepsis
 

19. Uterine exteriorization vs intraperitoneal repair at CS
Outcome: Blood transfusion
 

20. 3. Single vs double layer uterine closure
Cochrane review
2 RCTs, n=1006
No effect on endometritis or blood transfusions
Review of interventions considered:

21. Single vs two layer closure of uterine incision at CS
Outcome: Postpartum endometritis
 

22. Single vs two layer closure of uterine incision at CS
Outcome: Blood transfusion
 

23. 4. Uterine repair
•chromic catgut vs vicryl (polyglactin-910)
Cochrane review
No studies found
Review of interventions considered:

24. 4. Closure of both parietal and pelvioc peritoneum vs
non-closure
Cochrane review
10 RCTs, n=1761
Non-closure associated with less post-op fever
but no significant effect on wound infection or
endometritis
Review of interventions considered:

25. Non-closure of both parietal & visceral
peritoneum vs closure of both peritoneal layers
Outcome: Postoperative fever
 

26. Non-closure of both parietal & visceral peritoneum vs
closure of both peritoneal layers
Outcome: Endometritis
 

27. Non-closure of both parietal & visceral
peritoneum vs closure of both peritoneal layers
Outcome: Wound infection
 

28. 2 studies of long-term follow-up
Single vs double layer uterine closure
• 145 women out of 906 randomised
• followed up at time of next pregnancy
• no difference found between the groups (not surprisingly)
Chapman SJ, Owen J, Hauth JC. One versus two-layer closure of a low transverse
cesarean: the next pregnancy. Obstet Gynecol 1997; 89: 16-18.
Non-closure vs closure of peritoneum
• 144 women out of 280 randomised
• no differences found between the groups
Bahmanyar E, Boulvain M, Irion O. Non-closure of the peritoneum during cesarean
section: long-term follow-up of a randomized controlled trial. Am J Obstet Gynecol
2001; 185: S125.

29. Uterine exteriorisation vs intra-abdominal repair
- no diff for wound infection, sepsis, endometritis, blood
transfusion (less fever in exterioriorisation)
Single vs two layer uterine closure
- no difference for substantive outcomes
Chromic catgut vs polyglactin-910 (Vicryl) for uterine repair
- no studies identified
Closure vs non-closure of peritoneum
- no diff for wound infection or endometritis (less post-op fever in non-
closure)
Blunt vs sharp abdominal entry
- not enough evidence
Conclusions for 5 interventions for CORONIS

30. The CORONIS Trial
The CORONIS trial is funded by the UK
Medical Research Council in collaboration
with the World Health Organisation

31. The Trial
Collaborating countries
• Argentina
• Ghana
• India: two regions; Delhi and Vellore
• Kenya
• Pakistan
• Sudan
• 18 participating hospitals

32. Investigator Group
Chief Investigator Professor Peter Brocklehurst
Principal Investigators
Argentina Dr Edgardo Abalos
Ghana Dr Victor Addo
India: Delhi Dr Jai Sharma
India: Vellore Dr Jiji Mathews
Kenya Professor James Oyieke
Pakistan Dr Shabeen Masood
Sudan Professor Mohamed ElShiekh

33. Sample size
15,000 women world-wide
•At least 2000 women from each country
•All women followed-up 6 weeks after
discharge from hospital
•3 year recruitment period: 2007-2010
•Plans for 3 year follow-up of all women
recruited are underway

34. Study design
•The study is a multicentre, fractional factorial
randomised controlled trial.
•The collaborating institutions are centres with experience
in conducting trials.
•These centres also have experience in detailed follow-up
of large numbers of women.

35. Fractional, factorial design
In the CORONIS Trial five comparisons will be carried out
in one trial, using a 2x2x2x2x2 factorial design. Such a
design has rarely been used, but is appropriate for
the evaluation of several procedures which will be used
together in clinical practice.
In this trial of different caesarean section techniques, using
five pairs of possible allocated interventions (1 versus “not
1”, 2 versus “not 2”, 3 versus “not 3”, 4 versus “not 4”, 5
versus “not 5”), participants can receive one of 32 possible
alternatives.

36. Interventions
•Blunt versus sharp abdominal entry
•Exteriorisation of the uterus for repair versus
intra-abdominal repair
•Single versus double layer closure of the
uterus
•Closure versus non-closure of the peritoneum
(pelvic and parietal)
•Chromic catgut versus Polyglactin-910 for
uterine repair

37. Training in surgical techniques
•Training will vary between countries according to the
national standards of training in new surgical techniques
employed by each participating country. For example, if
the accepted standard for surgical training in a country is
that operators must perform a certain number of
procedures before they are judged to be competent in
that procedure, then this process should be followed.
•If, however, the national standard is that operators are
judged to be competent when a senior surgeon judges
them to be competent, then this process should be
followed. The accepted standard of surgical training in
each centre will be determined at the start of the trial.

38. • To facilitate training, a film of all the interventions being
tested in CORONIS will be provided to participating
centres. In individual countries, visits by the Regional
Co-ordinator to participating hospitals to teach specific
surgical techniques may be required so that experience
in the participating hospitals can be disseminated
rapidly.
• Participating centres will appoint a senior obstetrician to
ensure that only clinical staff competent in the various
surgical techniques to be used in the trial are ‘authorised’
to operate. A list of these personnel will be kept by the
local centre with a copy at the Regional Trial Office.
Training in surgical techniques

39. Primary outcome
Composite outcome of:
Death or maternal infectious morbidity
(one or more of the following: antibiotic
use for maternal febrile morbidity during
postnatal hospital stay, antibiotic use for
endometritis, wound infection or
peritonitis); or further operative
procedures; or blood transfusion.

40. Secondary outcomes
Clinical
• All components of the primary composite outcome as secondary outcomes
• Pain
• Interventions used for severe primary post-partum haemorrhage (PPH)
• Stillbirth after trial entry
• Apgar score < 3 at five minutes
• Laceration of baby at time of caesarean section
• Death of the baby by six weeks of age
• Other severe maternal morbidity
Health Service Utilisation
• Duration of operation (from incision to closure)
• Duration of hospital stay post-caesarean section
• Duration of stay in Intensive Care Unit post-caesarean section
• Number and duration of re-admissions to hospital within 6 weeks of
the caesarean section

41. Eligibility criteria
Women ARE eligible for trial entry if:
•they are undergoing delivery by lower
segment caesarean section through a
transverse abdominal incision, irrespective
of fever in labour, gestational age or
whether they have a multiple pregnancy.

42. Exclusion criteria
Women are NOT eligible if:
•there is a clear indication for a particular surgical
technique or material to be used that prevents
any of the allocated interventions being used,
e.g. for a woman with a previous vertical
abdominal incision it maybe considered
inappropriate to do a transverse abdominal
incision for this caesarean section. However, if a
transverse incision is going to be performed the
woman is eligible.

43. Women are NOT eligible if:
•they have had more than one previous
caesarean section.
•they have already been recruited into the
trial during a previous pregnancy
Exclusion criteria (cont.)

44. Informed consent
•Information leaflets will be made available to
local centres, in appropriate languages, which
explain the justification for the trial, the process
of trial entry and follow up.
•Once a woman becomes eligible, the trial should
be discussed with her (and her partner as
appropriate).
•A signed, or marked, consent form must be
provided before the woman is entered into the
trial.

45. Data collection
•At study entry
•Immediately following delivery
•During the postpartum stay in hospital
•At 6 weeks after discharge from hospital
•Data Collection Booklets contain all the
necessary data collection forms

46. International Co-ordinating
Team
Chief Investigator Peter Brocklehurst
Trial Statistician Ed Juszczak
Trial Director Barbara Farrell
IT Co-ordinator Patsy Spark
Study Administrator Shan Rich

47. International Co-ordinating
Centre
National Perinatal Epidemiology Unit
University of Oxford
www.npeu.ox.ac.uk/CORONIS