van Beekhuizen 2006.

Methods	• Trial design: The Netherlands. Multicentric randomised clinical trial, parallel, 2 arms.   • Funding sources reported: not mentioned.   • Ethical issues: use of signed informed consent and ethics approval.
Participants	• Inclusion and exclusion criteria   Exclusion criteria: Blood loss ≥ 1000 mL. Reduction in diastolic blood pressure ≥ 20 mmHg. Tachycardia ≥ 120 beat/minutes. Gynaecologic infection. General history. Age < 18 or > 40 years. Gestational age ≥ 28 weeks. Asthma, bronchitis. Epilepsy. Cardiac disease. Hypertension, pre‐eclampsia, HELLP syndrome. Liver failure, renal failure. Stomach ulcer, ulcerative colitis. Sickle cell anaemia, b‐thalassaemia. Glaucoma.   • Study participants were recruited from women who were admitted for hospital delivery and from women who had been referred because of retained placenta after home delivery.   • Women who were delivered in the hospital all received active management of labour with oxytocin 10 IU intramuscularly, and controlled cord traction. The women who were referred because of retained placenta after home delivery received the same treatment after they had arrived in the hospital. The administration of study medication started 60 minutes after the delivery of the Infant.
Interventions	• Total number of intervention groups: 2 groups.   Intervention: sulprostone (synthetic prostaglandin‐E2 derivative) 250 mg by 30 minutes of intravenous infusion. Single doses. 24 participants.   Control: placebo by 30 minutes of intravenous infusion. Single doses. 26 participants.
Outcomes	• The primary outcome was the presence or absence of manual removal of placenta.   • The secondary outcome variable was the amount of blood loss (mL). The amount of in‐hospital blood loss was determined by weight; blood loss before entering the hospital was estimated by the referring midwife. Adverse event reports (shivering, headache, pain, vomiting and nausea, hypotension and hypertension) were recorded and measured subjectively.
Notes	Correspondence: yes. We send a letter asking to the principal author about the method implemented in the study in order to blind the study participants and personnel. We used an open question.   The author answered: "The RCT was double blinded: After the patient was recruited a sealed enveloped was handed to an 'independent' midwife who was not involved in taking care of the patient. She opened the envelope and prepared the study medication and handed the blinded study medication to the midwife/nurse who took care of the patient. This was to ensure that both the patient, the doctor and the midwife were not aware whether the patient received placebo or study medication". Comment: unclear risk for performance and detection bias.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“…Study medication was randomised in blocks of 4…” Comment: probably done.
Allocation concealment (selection bias)	Low risk	“…the allocation of sealed envelopes was in the sequence of enrolment…” Comment: probably done.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Did not adequately reported the method implemented to blind study participants and personnel from knowledge of which intervention a participant received “…The physician in charge was blinded to the trial medication…” Comment: unclear risk of bias.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Did not adequately reported the method implemented to blind study participants and personnel from knowledge of which intervention a participant received “…The physician in charge was blinded to the trial medication…” Comment: unclear risk of bias.
Incomplete outcome data (attrition bias) All outcomes	High risk	Authors did a “As‐treated” analysis because they only included the results from those women who had both been assigned randomly and who had actually received the trial medication.
Selective reporting (reporting bias)	Unclear risk	The report did not have sufficient information to permit judgment of “Yes” or “No”.
Other bias	High risk	Stopped early rule due to apparent benefit.