Atosiban Evidence Based Medicine

8/14/2019 Atosiban Evidence Based Medicine

1/23

An oxytocin receptor antagonist (atosiban)

in the treatment of preterm labor: Arandomized, double-blind, placebo-controlled trial with tocolytic rescue

Roberto Romero, MD, Baha M. Sibai, MD, Luis Sanchez-Ramos, MD, Guillermo J.Valenzuela, MD, Jean-Claude Veille, MD, Bannie Tabor, MD, Kenneth G. Perry,MD, Michael Varner, MD, T. Murphy Goodwin, MD, Rosanne Lane, MAS, JudithSmith, PhD, Gary Shangold, MD, and George W. Creasy, MD


2/23

Atosiban

selective oxytocin-vasopressin receptor

antagonist capable of inhibiting oxytocin-induced uterine contractions in women with

preterm labor.


3/23

Evaluating Directness


4/23

Clinical Question

Among pregnant woman, how effective is

oxytocin receptor antagonist (atosiban)compared to placebo in preventingpreterm labor?


5/23

Clinical Question

Population Pregnant woman in preterm labor (20-33 wks AOG)

Exposure oxytocin receptor antagonist (atosiban) compared to placebo

Outcome Treatment of preterm labor


6/23

Appraising Validity


7/23

Were patients randomly assignedto treatment groups?

Yes, Patients were randomly assigned to

receive intravenous therapy with atosiban or

matching placebo.


8/23

Was allocation concealed?

Yes, Prenumbered randomization envelopes

provided to the pharmacist at each study

center were to be opened in sequential order.


9/23

Were baseline characteristics similarat the start of the trial?

Yes, The baseline demographic and clinical

characteristics of patients in both groups are

displayed in Table I,( p5). The treatment

groups were comparable for most baseline

variables including race, maternal age, and

parity.


10/23

Were patients blinded to treatmentassignment?

Yes, Investigators, study personnel, and

monitors remained blinded throughout

the study.


11/23

Were caregivers blinded to treatmentassignment?

Yes, Investigators, study personnel, and

monitors remained blinded throughout the

study.


12/23

Were all patients analysed in the groupsto which they were originally randomized?

Yes. For efficacy, the primary intent-to-treat analyses were

performed on the basis of all patients who received study drug. The

attrition rate in this study was minimal (6%); therefore from a

clinical perspective the results from the population of patients who

received study drug are most meaningful. However, intent-to-treat

analyses including all patients randomized were performed. The

results of the intent-to-treat analyses of both populations led to the

same conclusion, but only the results for patients who received

study drug are provided.


13/23

Was follow-up rate adequate?


14/23

Appraising the Results


15/23

How large was the effect of treatment?

Placebo (n=255) Atosiban (n=246)

Proportion % Proportion % Difference 95%confidenceinterval

7d

28wk 220-105/220

52 203-131/203

35 17% (7% to26%)


16/23

How large was the effect of treatment?

RRR=

Rc Rt

Rc

ARR= Rc Rt RR = Rt

Rc

Interpretation

7d

28wk 52-35

52=33%

52-35

= 17%

35 =0.67

52

Treatment

beneficial


17/23

How precise was the estimateof the treatment effect?

RRR

Rc Rt

Rc

Interpretation

7d

28wk 52-35

52

=33%

Atosiban prevents preterm

labor by 33% but the actualRRR could range to 7% to

26%

Treatment(Atosiban)

surely better thancontrol (placebo)

(95% CI: 34.32)


18/23

Assessing applicability


19/23

Are there biological issues that may affect applicabilityof treatment? (Considering the influence of sex,co-morbidity, race age and pathology).

Yes, patient should be in a gestational age of 20 weeks to 33

weeks 6 days with live fetus(es). Patients were excludedfrom participation if they had any of the following: fetal or

placental abnormalities, fetal distress, suspected

chorioamnionitis, maternal indications for delivery, urinarytract infection, and overt clinical manifestations of

substance abuse.


20/23

Are the socio-economic issues affectingapplicability of the treatment?

None


21/23

Individualizing the results


22/23

What is the likely effect of the treatment onyour individual patient? (Estimate theindividualized NNT for your patient)

7d Interpretation

28 weeks100/83= 17 You need to treat 17

patients to prevent

preterm labor with

Atosiban


23/23

Are the benefits to your patients worththe harm and costs?

Benefit Atosiban prevents preterm labor upto 7 days if AOG is >28 weeks.

Harm Atosiban is not effective inpreventing preterm labor if AOG is

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Atosiban Evidence Based Medicine