An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: A randomized, double-blind, placebocontrolled 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, Judith Smith, PhD, Gary Shangold, MD, and George W. Creasy, MD

Atosiban
selective oxytocin-vasopressin receptor antagonist capable of inhibiting oxytocin-

induced uterine contractions in women with

preterm labor.

Evaluating Directness

Clinical Question
Among pregnant woman, how effective is oxytocin receptor antagonist (atosiban) compared to placebo in preventing preterm labor?

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

Appraising Validity

Were patients randomly assigned to treatment groups?

Yes, Patients were randomly assigned to receive intravenous therapy with atosiban or

matching placebo.

Was allocation concealed?

Yes, Prenumbered randomization envelopes

provided to the pharmacist at each study

center were to be opened in sequential order.

Were baseline characteristics similar at 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.

Were patients blinded to treatment assignment?

Yes, Investigators, study personnel, and monitors remained blinded throughout

the study.

Were caregivers blinded to treatment assignment?

Yes, Investigators, study personnel, and monitors remained blinded throughout the study.

Were all patients analysed in the groups to 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.

Was follow-up rate adequate?

Appraising the Results

How large was the effect of treatment?

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

Proportion

Proportion %

Difference

95% confidence interval

7d

<28wk

34-20/34

41

43-22/43

49

-8%

(-31% to 16%)
(7% to 26%)

>28wk

220105/220

52

203131/203

35

17%

How large was the effect of treatment?

RRR= Rc Rt Rc 7d <28wk ARR= Rc Rt

RR = Rt Rc

Interpretation

41-49 41 =-20%

41-49 =-8

49 =1.2 41

Treatment harmful

>28wk

52-35 52 =33%

52-35 = 17%

35 =0.67 52

Treatment beneficial

How precise was the estimate of the treatment effect?

RRR Rc Rt Rc

Interpretation

7d
<28wk 41-49 41 = -20% >28wk 52-35 52
Atosiban prevents preterm Treatment surely labor by -20% but the worse than control actual RRR could range to 31% to 16% (95% CI: -21%, -19%) Atosiban prevents preterm Treatment(Atosiban) labor by 33% but the actual surely better than RRR could range to 7% to control (placebo) 26%

=33%

(95% CI: 34.32)

Assessing applicability

Are there biological issues that may affect applicability of 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 excluded

from participation if they had any of the following: fetal or placental abnormalities, fetal distress, suspected

chorioamnionitis, maternal indications for delivery, urinary

tract infection, and overt clinical manifestations of substance abuse.

Are the socio-economic issues affecting applicability of the treatment?

None

Individualizing the results

What is the likely effect of the treatment on your individual patient? (Estimate the individualized NNT for your patient)
7d
<28 weeks

Interpretation You need to harm 13 patients to prevent preterm labor with Atosiban You need to treat 17 patients to prevent preterm labor with Atosiban

100/-8= -13

>28 weeks

100/83= 17

Are the benefits to your patients worth the harm and costs?
Benefit Harm
Atosiban prevents preterm labor up to 7 days if AOG is >28 weeks. Atosiban is not effective in preventing preterm labor if AOG is <28 weeks Atosiban is not available in the Phillipines. US price $90 (P 3780) per 6.75 mg/0.9 ml solution for injection

Cost