Skvortsova 2004.

Study characteristics
Methods	Study design: RCT Study grouping: parallel‐group Losses to follow‐up: none Trial protocol registration: no protocol identified
Participants	Cerebrolysin Participants: 12 Men: 6 Women: 6 Mean age: 68.7 years ± 10.6 Ratio of participants with lesions of the left and right hemispheres: 8/4 Period since the stroke to admission in hospital: 9.2 hours ± 2.9 NIHSS score prior to intervention: 11.2 ± 4.7 Rankin score prior to intervention: 3.5 ± 1.1 Number of participants with an NIHSS score more than 14 (severe stroke): 3 (25%); 14 and less: 9 (75%) Average volume of brain lesions: 17.5 cm3 ± 14.7 Number of participants with a lesion volume between 7 cm3 and 64 cm3: 8 Placebo Participants: 12 Men: 9 Women: 3 Mean age: 69.4 years ± 9.5 Ratio of participants with lesions of the left and right hemispheres: 8/4 Period since the stroke to admission in hospital: 8.6 hours ± 2.9 NIHSS score prior to intervention: 12.2 ± 2.8 Rankin score prior to intervention: 3.8 ± 0.9 Number of participants with an NIHSS score more than 14 (severe stroke): 3 (25%); 14 and less: 9 (75%) Average volume of brain lesions: 21.7 cm3 ± 23.1 Number of participants with a lesion volume between 7 cm3 and 64 cm3: 7 Inclusion criteria: people with first‐in‐lifetime ischaemic stroke in the basin of internal carotid artery, aged 45 to 85 years, admitted to the ICU within 12 hours of stroke symptoms onset Exclusion criteria: disappearance of symptoms within 4 hours from the beginning of stroke; people with haemorrhagic stroke or stroke in the vertebrobasilar system; people with blood pressure levels higher than 200/100 mmHg; people with acute myocardial infarction, with a priori severe dementia; pregnant women; and participants in other studies Pretreatment: no difference
Interventions	Cerebrolysin Frequency of dosage: diluted with 40 mL of saline infused by slow drip over 1 hour for 10 days after stroke onset (within 12 hours) Standard treatment: aspirin 100 mg/day, haemodilution, pentoxifylline, heparin (when needed) Placebo Frequency of dosage: physiological saline Standard treatment: aspirin 100 mg/day, haemodilution, pentoxifylline, heparin (when needed)
Outcomes	Poor functional outcome defined as death or dependence at the end of the follow‐up period (dichotomous outcome) Early death (dichotomous outcome) All‐cause death (dichotomous outcome) Serious adverse events (dichotomous outcome) Adverse effects specifically associated with Cerebrolysin (dichotomous outcome) Total number of participants with adverse events (dichotomous outcome)
Identification	Sponsorship source: not reported Country: Russia Setting: inpatient Author's name: Skvortsova Institution: Department of Basic and Clinical Neurology, Russian State Medical University Address: Moscow
Notes	No study protocol identified
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment	Unclear risk	Quote: "Всем пациентам рандомизированно и вслепую было назначено плацебо или церебролизин в дозе 10 либо 50 мл (по 12 человек в каждой группе)." ["Vsem patsiyentam randomizirovanno i vslepuyu bylo naznacheno platsebo ili tserebrolizin v doze 10 libo 50 ml (po 12 chelovek v kazhdoy gruppe)"]: "All patients were randomly and blindly assigned to placebo or Cerebrolysin at 10 or 50 mL (12 in each group)." Comment: insufficient information to permit a judgement of low risk or high risk. There was no mention of allocation concealment. In addition to the unavailability of a study protocol, we judged this as an unclear risk.
Sequence generation	Unclear risk	Quote: "Всем пациентам рандомизированно и вслепую было назначено плацебо или церебролизин в дозе 10 либо 50 мл (по 12 человек в каждой группе)." ["Vsem patsiyentam randomizirovanno i vslepuyu bylo naznacheno platsebo ili tserebrolizin v doze 10 libo 50 ml (po 12 chelovek v kazhdoy gruppe)"]: "All patients were randomly and blindly assigned to placebo or Cerebrolysin at 10 or 50 mL (12 in each group)." Comment: there was no information on allocation concealment. In addition to the unavailability of a study protocol, we judged this as an unclear risk.
Incomplete outcome data All outcomes	Low risk	Quote: "Анализ исходов инсульта к 30‐м суткам не обнаружил достоверных различий между группами в летальности. Причины смерти 3 из 5 больных, получавших церебролизин, а также одного пациента из группы плацебо не были связаны с инсультом (тромбоэмболия легочной артерии, пневмония, пиелонефрит). У 2 пациентов, получавших церебролизин, и 2 получавших плацебо смерть наступила вследствие отека мозга с развитием вторичного стволового синдрома." ["Analiz iskhodov insul’ta k 30‐m sutkam ne obnaruzhil dostovernykh razlichiy mezhdu gruppami v letal’nosti. Prichiny smerti 3 iz 5 bol’nykh, poluchavshikh tserebrolizin, a takzhe odnogo patsiyenta iz gruppy platsebo ne byli svyazany s insul’tom (tromboemboliya legochnoy arterii, pnevmoniya, piyelonefrit). U 2 patsiyentov, poluchavshikh tserebrolizin, i 2 poluchavshikh platsebo smert’ nastupila vsledstviye oteka mozga s razvitiyem vtorichnogo stvolovogo sindroma.": "Analysis of stroke outcomes by day‐30 did not uncover significant differences between groups in lethality. The causes of death of 3 out of 5 patients, treated with Cerebrolysin, and one patient from the placebo group were not attributed to stroke (pulmonary oedema, pneumonia, pyelonephritis). In 2 patients, treated with Cerebrolysin, and 2 treated with placebo, deaths occurred due to cerebral oedema with development of secondary brain stem syndrome."] Comment: no losses to follow‐up, causes of death described. However, adverse events were not reported and the study protocol was not available.
Blinding of outcome assessors All outcomes	Unclear risk	Comment: there was no information on blinding of outcome assessors. In addition to the unavailability of a study protocol, we judged this as an unclear risk.
Selective outcome reporting	Unclear risk	Comment: study protocol not available; we judged this as an unclear risk. Quote: "Причины смерти 3 из 5 больных, получавших церебролизин, а также одного пациента из группы плацебо не были связаны с инсультом (тромбоэмболия легочной артерии, пневмония, пиелонефрит)". ["Prichiny smerti 3 iz 5 bol’nykh, poluchavshikh tserebrolizin, a takzhe odnogo patsiyenta iz gruppy platsebo ne byli svyazany s insul’tom (tromboemboliya legochnoy arterii, pnevmoniya, piyelonefrit).": "The causes of death for 3 of 5 patients who received Cerebrolysin and 1 patient in the placebo group were not associated with stroke (pulmonary embolism, pneumonia, pyelonephritis)".] Comment: the time when deaths occurred was not reported. Furthermore, the study authors considered that deaths were not drug‐related. Adverse events were not reported. The timing was not clear for outcomes presented in a table and a graph, although these outcomes were not those of interest for the review.
Blinding of participants and personnel All outcomes	Unclear risk	Quote: "Всем пациентам рандомизированно и вслепую было назначено плацебо или церебролизин в дозе 10 либо 50 мл (по 12 человек в каждой группе)". ["Vsyem patziyentam randomizirovanno i vslyepooyo bilo naznachyeno platzyebo ili tzyeryebrolizin v dozye 10 libo 50 ml (po 12 chyelovyek v kaʐdoy gurooppye).": "All patients were randomly and blindly assigned to placebo or Cerebrolysin at 10 or 50 mL (12 in each group)."] Comment: there was no information on blinding of participants and personnel. In addition to the unavailability of a study protocol, we judged this as an unclear risk.
Other sources of bias	Unclear risk	Comment: no information on funding sources for the trial, and no conflict of interest statement was provided. No study protocol available.