Landmark Trials Flashcards
Results of RCT planned CS vs VB for twins
No evidence that planned CS improved perinatal outcomes
What is the TRUFFLE trial?
Two year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm FGR
TRUFFLE Trial - type of study
Prospective multi centre unblinded randomised study
Number of participants in the TRUFFLE trial
503
What is the MAGPIE trial?
Do women with PET, and their babies, benefit from MgSO4?
Results of MAGPIE trial
Significantly fewer eclamptic seizures with MgSO4, NNT 91
Results of Cochrane review of magnesium sulfate for women at risk of PTB for neuroprotection
Decreased cerebral palsy - RR 0.68, NNT 63 (NNT 29 if <28wks)
Decreased gross motor dysfunction - RR 0.61
What is the CLASP trial?
Randomised trial of low dose aspirin for the prevention of preeclampsia among 9364 pregnant women
Intervention for CLASP trial?
60mg aspirin or placebo from 12 weeks or from randomisation
Full name of PPROMT Trial
Immediate delivery compared with the expectant management after PROM close to term
Primary outcome of PPROMPT trial
Neonatal sepsis
Results of PPROMPT Trial
No difference in neonatal sepsis (2% vs 3%)
Increased RDS and NICU admission in IOL group
Increased CS rate in IOL group
Increased APH and maternal fever with expectant group
How many women were included in the WHI RCT: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy (2004)
10,700
Inclusion criteria for the WHI RCT: Effects of conjugated equine estrogen in PM women with hysterectomy
PM women age 50-79 with previous hysterectomy
What was the primary outcome for WHI RCT: Effects of conjugated equine estrogen in PM women with hysterectomy?
CHD - MI or CHD death
Secondary outcomes: Stroke, VTE, cancer and fractures
Results of WHI RCT: Effects of conjugated equine estrogen in PM women with hysterectomy
Trial stopped early
Increased risk of stroke and VTE
Decreased breast Ca risk in treatment group
Decreased fractures in treatment in treatment group
Provision of no cost LARCs and teenage pregnancy, Secura et al 2014
Type of study?
Prospective cohort study, followed for 2-3 years
Provision of no cost long acting contraception and teenage pregnancy
Inclusion criteria
1404 of the adolescents enrolled in the CHOICE study, aged between 14-19 years
Who published the Provision of no cost LARCs and teenage pregnancy study?
When?
Secura et al, 2014
Ovarian conservation at time of hysterectomy for benign disease, 2005
Type of study
Retrospective case control study using Markov decision making modelling
Ovarian conservation at time of hysterectomy for benign disease, 2005
Primary outcome
Mortality / long term survival
Breast and ovarian cancer
Ovarian conservation at time of hysterectomy for benign disease, 2005
Results
Ovarian conservation to age 65 benefits long term survival
- at no age is there a clear benefit for opohorectomy for survival
BSO: Increases all cause mortality, decreased breast and ovarian cancer
A Comparison of Medical Management with Misoprostol and Surgical Management for Early Pregnancy Loss, 2005
Type of study
RCT
652 women (randomised 3:1 to miso)
A Comparison of Medical Management with Misoprostol and Surgical Management for Early Pregnancy Loss, 2005
Inclusion criteria
Missed or incomplete miscarriage
A Comparison of Medical Management with Misoprostol and Surgical Management for Early pregnancy loss, 2005
Primary outcome
No need or evacuation within 30 days
Secondary outcomes: Hb drop, unplanned trip to hospital, haemorrhage
Results of A Comparison of medical management with misoprostol and surgical management for early pregnancy loss
84% success rates with Misoprostol vs 97% with Evacuation
- lower success for medical with anembryonic pregnancy
- no difference in haemorrhage or infection
- 5% misoprostol vs 1% evacuation had Hb drop of >30
Conclusion of A Comparison of Medical Management with Misoprostol vs Surgical Management for Early Pregnancy Loss
Complications from misoprostol: Rate <1:70
83% would recommend it
Primary Outcome of the ALIFE trial
Rate of live birth
Secondary outcome = Gestation at delivery
Results of the ALIFE trial
No difference in primary outcome
Those on LMWH + Aspirin delivered ~1 week earlier
ALIFE Trial
Full name of trial
Aspirin + Low Molecular Weight Heparin or Aspirin Alone in Women with Recurrent Miscarriage
ALIFE Trial - type of study
Multicentre, double blinded, placebo controlled RCT
364 women (84% became pregnant)
ALIFE Trial - Inclusion criteria
2 or more unexplained miscarriages >20/40
ALIFE Trial - intervention
3 arms:
- 80mg Aspirin + LMWH from 6/40
- 80mg only
- Placebo
SPIN Study - Full name of study
Scottish Pregnancy Intervention Study:
RCT of LMWH + Low Dose Aspirin in Women with Recurrent Miscarriage
SPIN Study - Type of study
Multicentred ?double-blinded RCT
294 women
SPIN Study - Inclusion criteria
2x consecutive pregnancy losses (most recent pregnancies) <24/40
Presenting for antenatal care <7/40SP
SPIN Study
Intervention
75mg Aspirin + 40mg LMWH + Intensive monitoring
Vs
Intensive monitoring
WHI RCT: Risks and Benefits of Oestrogen + Progestin in Healthy Post-menopausal Women, Principal Results, 2002
Type of study
Multicentre, placebo controlled, RCT
16,600 women
WHI RCT: Risks and Benefits of Oestrogen + Progestin in Healthy Post-menopausal Women, Principal Results, 2002
Inclusion criteria
PM women aged 50-79 with intact uterus
WHI RCT: Risks and Benefits of Oestrogen and Progestin in Healthy PM women, Principal results 2002
Intervention
Conjugated equine oestrogen 0.625mg/d + Provera 2.5mg/d
vs
Placebo
WHI RCT: Risks and Benefits of Oestrogen + Progestin in Healthy PM Women, Principal Results, 2002
Primary Outcomes
Coronary heart disease - acute MI or death due to CHD
Secondary outcomes = Stroke, VTE, Cancer, Fractures
WHI RCT: Risks and Benefits of Oestrogen + Progestin in Healthy PM Women, Principal Results, 2002
Results
Trial stopped early
Increased CHD
VTE risk doubled
Increased invasive breast Ca
Decrease in colorectal cancer and hip fractures
Limitations of WHI RCT?
Average age 63
Not appropriately assessed for baseline risk - high rates of obesity, HTN, smoking
Only 1 dose/route of HRT
High rates of crossover and discontinuation
PLCO Study - Full name
Effect of Screening on Ovarian Cancer Mortality
- The Prostate, Lung, Colorectal and Ovarian (PLCO) Screening RCT
PLCO Study
- When was it published?
2011
PLCO Study - type of study
Large multicentre RCT
34000 in each arm
PLCO Study
Inclusion criteria
55-74 years old, no previous dx of lung, colorectal or ovarian cancer
PLCO Study - Intervention
Annual Ca125 + TV Pelvic USS
PLCO - Primary Outcome
Ovarian cancer specific mortalitySP
SPIN Study - Primary outcome
Loss of index pregnancy
Results of SPIN Study
No difference in primary outcome
No complications of treatment
LACE Trial - Full name of trial
Effect of TAH vs TLH on Disease Free Survival Among Women with Stage 1 Endometrial Cancer
LACE Trial - Type of trial
International, multicentre RCT
What was the primary outcome of the LACE Trial?
Disease free survival
Secondary outcomes: Recurrent endometrial cancer and overall survival
LACE Trial
Results?
No difference in primary outcome
No difference in overall survival, surgical risks or QoL
Limitations of the LACE Trial
11% lost to follow up, skill of surgeons
PLCO Study - Secondary outcomes
Ovarian cancer incidence, cancer stage, survival, all cause mortality, harms of screening
Results of PLCO Study
No difference in primary outcomes
No difference in all cause mortality
Increased rates of oophorectomy in screened group - high number of false positives
Strengths and Limitations of the PLCO Study
Strengths: Multicentre, randomised
Limitations: 13% non-compliant with screening, some in control group received screening outside of trial
Conclusion of PLCO Study
Screening intervention not effective at reducing cause specific mortality
Screening increased invasive procedures and associated harms
Million Women Study - What is the full name of the study?
Breast cancer and HRT in the Million WOmen Study
Million women study - type of trial
Cohort study
- age 50-64 years
Million women study - inclusion criteria
Age 50-64
Recruited at time of triennial breast screening
Million women study - primary outcome
First diagnosis of invasive breast cancer and attributable deaths
Million women study - results
Increased risk of breast cancer in current users (RR 1.66) not in past users.
No increased risk if stopped >5yrs.
RR for estrogen only = 1.3
RR for E+P = 2.0
+5 per 1000 oestrogen only if used >10yrs
+19 per 1000 combined if used >10yrs
Strengths and Limitations of the Million Women Trial
Strengths = Large
Limitations = Poor selection as recruited at screening (likely higher health literacy, SES etc), assumptions made about menopausal status
When was the MAGPIE Trial published?
2002
What is the full name of the MAGPIE trial?
Do women with pre-eclampsia, and their babies, benefit from MgSO4?
MAGPIE - Type of trial
International multicentre, placebo controlled, double blinded RCT
Included over 10,000 women
What was the conclusion of the TRUFFLE Trial?
Timing of delivery based on late DV changes (absent a-wave) MAY improve neurodevelopment at 2 years
Strengths and limitations of the TRUFFLE Trial?
Strengths: Randomised, multicentre
Limitations: Unblinded
Delivery sometimes required for maternal reasons or based on obvious CTG changes (not STV)Pr
Progesterone and the risk of preterm birth among women with a short cervix, 2007
Type of study?
Multicentre, double blinded, placebo controlled RCT
250 patients in study (but over 24000 screened)
Progesterone and the risk of preterm birth among women with a short cervix, 2007
Inclusion criteria
Cervix =/< 15mm on mid-trimester USS 20-25/40, irrespective of previous history
Primary outcome for Fonseca et al study published in 2007
Preterm birth <34/40
(progesterone and the risk of pre-term birth among women with a short cervix)
Progesterone and the risk of preterm birth among women with a short cervix, 2007
Results
Reduction in PTB <34/40
19% vs 34% (RR 0.56)
Strengths and limitations of Progesterone for Short cervix trial in 2007?
Strengths - randomised, double blinded and placebo controlled –> low risk of bias.
Sufficiently powered
Limitations: Small, different dose of progesterone used compared to previous RCT (200mg vs 100mg)
When was the TERM PROM trial published?
1996
TERM PROM, 1996
Full name
Induction of labour compared with expectant management for prelabour rupture of membranes at term
TERM PROM - interventions
4 arms
Immediate IOL with either synto or PG
Expectant mgt with IOL at 4 days or when indication arose
- either synto or PG
TERM PROM - inclusion criteria
PROM >37 weeks with cephalic singletone
- excluded if in active labour, or contraindication to any treatment (e.g chorio or meconium liquor)
ACHOIS Trial - Primary outcome
Infants: Death, shoulder dystocia, fracture, nerve palsy, NICU admission and jaundice
Mothers: IOL, C/S, psych outcomes and QoL
ACHOIS Trial - Results
Decreased rate of serious perinatal outcomes in treatment group (4% to 1%, NNT 34)
Decreased macrosomia, increased NICU admissions
Maternal: Increased IOL rate, same C/S rate, decreased depression in treatment group
Limitations of ACHOIS trial
Not blinded
Possible bias due to increased clinician awareness
Groups not homogenous
What was the aim of the ARRIVE trial
To test whether IOL at 39 weeks would result in lower risk of perinatal death or severe neonatal complication, than expectant management in low risk nulliparous women
ARRIVE Trial - type of study
Multicentred, parallel group, unmasked RCT
6106 women
ARRIVE trial - inclusion criteria
Low risk nulliparous women 34-38+6 at time of enrollment
Singleton, cephalic, with no contraindication to NVD
Oracle 1 Trial - Full name of study
Broad spectrum antibiotics for preterm pre-labour rupture of membranes
Oracle 1 Trial - intervention
Erythromycin
Augmentin
Both
Neither
For 10 days
What were the primary and secondary outcomes of the ARRIVE Trial?
Primary outcome: Composite of perinatal death or severe neonatal complications
Secondary outcome = C/S rate
ARRIVE Trial - Results
No significantly decreased risk of primary outcome (perinatal death or severe neonatal complications)
Significantly reduced rate of C/S in IOL group (18.6% vs 22.2%)
Women reported increased satisfaction and feeling of control in IOL group
Strengths and limitations of the ARRIVE trial
Strengths - study design, large size
Limitations: Doesn’t reflect how we practice in NZ (LMC vs obs lead)
Different IOL methods
Not blinded
WOMAN Trial, 2017 - Name of study
Effect of early TXA administration on mortality, hysterectomy and other morbidities in women with PPH
WOMEN Trial - type of study
International double blinded, placebo controlled RCT
20,000 participants
WOMAN trial - inclusion criteria
PPH 500ml after VB, or 1000ml after C/S, or EBL enough to cause haemodynamic instability
What was the primary outcome in the ORACLE 1 trial
Composite of neonatal death, chronic lung disease, and major cerebral abnormality
Results of ORACLE I Trial?
Erythromycin decreased primary outcome but not statistically significant
Significant prolongation of pregnancy and decreased surfactant and O2 use
Increased NEC with Augmentin
HYPITAT Trial, 2009
- Name of study
Induction vs Expectant management for gestation HTN or mild PET after 36 weeks
HYPITAT Trial, 2009
- Inclusion criteria
36-41/40
Singleton cephalic
Gestational HTN with diastolic BP >95 or mild PET with diastolic BP >90 and proteinuria
Excluded severe hypertension 170/110, severe PET, HELLP, pre-existing HTN
HYPITAT Trial, 2009,
- Intervention
IOL within 24hrs
vs
Expectant mgt with monitoring, if no severe HTN - IOL >41/40
ACHOIS Trial, 2005 - Name of trial
Effect of treatment of GDM on pregnancy outcomes
ACHOIS Trial, 2005 - Intervention
Routine ANC
vs
GDM care with education, dietary advice, BSL monitoring and targets, plus insulin as needed
HYPITAT Trial - Primary outcome
Composite measure of poor maternal outcome (death, morbidity, progression to severe disease)
HYPITAT Trial - Results
Primary outcome decreased in IOL group (RR 0.71), NNT = 8
–> mainly due to less progress to severe disease
Benefit of IOL not present <37/40
No difference in neonatal outcomes
Planned C/S or VB for Twins 2013
- Primary outcomes
Composite fetal / neonatal morbidity and mortality
Composite maternal morbidity and mortality
HAPO Study - Primary outcomes
Birth weight >90th%
C/S
Neonatal hypoglycaemia
Cord c-peptide levels
HAPO Study - Results
With increase in maternal glucose results = increase in each primary outcome
- Birth weight >90th% and c-peptide levels = Strong association
- C/S and neonatal hypoglycamia = Weaker association
