E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of haemorrage during surgery |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of bleeding resulting from surgery |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physical Phenomena [G01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objectives of this study are to evaluate the efficacy and safety of Fibrin Sealant Grifols (FS Grifols) as an adjunct to achieve hemostasis during surgery in pediatric subjects.
Primary Efficacy Objective
• To evaluate if FS Grifols is non-inferior to EVICEL® in terms of the proportion of subjects achieving hemostasis at the target bleeding site (TBS) by 4 minutes (T4) from the start of treatment application (TStart) with no occurrence of rebleeding until the completion of the surgical closure by layers of the exposed surgical field containing the TBS (TClosure).
Safety Objective
To evaluate the safety and tolerability of FS Grifols in pediatric subjects undergoing surgery |
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E.2.2 | Secondary objectives of the trial |
Secondary Efficacy Objectives
• To determine the cumulative proportion of subjects achieving hemostasis at the TBS by the defined observation time points of 7 minutes (T7) and 10 minutes (T10) from TStart
• To determine prevalence of treatment failures
Exploratory Efficacy Objectives
• To determine the proportion of subjects achieving at least 1 point decrease in bleeding intensity according to the 5-point validated bleeding severity scale by the defined observation time points of T4, T7, and T10
• To determine the mean change from baseline in bleeding intensity according to the 5 point validated bleeding severity scale at the defined observation time points of T4, T7, and T10
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria:
A subject must meet all the following inclusion criteria to be eligible for participation in this study.
Pre-operative:
1. Is less than 18 years of age.
2. Requires an elective (non-emergent), open (non-laparoscopic), pelvic, abdominal, or thoracic (non-cardiac) surgical procedure.
3. Subject and/or subject’s legal guardian is willing to give permission for the subject to participate in the clinical trial and provide written informed consent for the subject. In addition, assent must be obtained from pediatric subjects who possess the intellectual and emotional ability to comprehend the concepts involved in the clinical trial.
Intra-operative:
4. Presence of an appropriate (as defined in inclusion criterion 5) parenchymous or soft tissue TBS identified intra-operatively by the investigator (the surgeon).
5. TBS has Grade 1 (mild) or Grade 2 (moderate) bleeding intensity according to the investigator’s (the surgeon’s) judgment. The intensity of the bleeding at the TBS will be rated by the investigator using the 5-point validated bleeding severity scale.
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E.4 | Principal exclusion criteria |
A subject meeting any of the following exclusion criteria is NOT eligible for participation in the study.
Pre-operative:
1. Subjects admitted for trauma surgery.
2. Subjects unwilling to receive blood products.
3. Subjects with known history of severe (eg, anaphylactic) reaction to blood products.
4. Subjects with known history of intolerance to any of the components of the investigational product (IP).
5. Female subjects who are pregnant, breastfeeding or, if of child-bearing potential (ie, adolescent), unwilling to practice a highly effective method of contraception (eg, oral, injectable, or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study.
True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.).
6. Subjects previously enrolled in a clinical trial with FS Grifols.
7. Subjects currently participating, or during the study is planned to participate, in any other investigational device or medicinal product study.
Intra-operative:
8. An appropriate parenchymous or soft tissue TBS (as defined in exclusion criteria 9 and 10) cannot be identified intra-operatively by the investigator (the surgeon).
9. The TBS has Grade 3 (severe) bleeding according to the investigator’s (the surgeon’s) judgment that cannot be controlled with conventional surgical techniques to Grade 1 or Grade 2 bleeding. The intensity of the bleeding at the TBS will be rated by the investigator using the 5-point validated bleeding severity scale.
10. The TBS is in an actively infected surgical field.
11. Occurrence of major intra-operative complications that require resuscitation or deviation from the planned surgical procedure.
12. Application of any topical hemostatic agent on the resection surface of parenchyma or soft tissue prior to application of the IP.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint in this clinical trial is the proportion of subjects achieving hemostasis at the TBS by T4, with no occurrence of rebleeding until the completion of the surgical closure by layers of the exposed surgical field containing the TBS (TClosure). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
T4: 4 minutes after start of treatment application |
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E.5.2 | Secondary end point(s) |
• Cumulative proportion of subjects achieving hemostasis at the TBS by the defined observation time points of T7 and T10
• Prevalence of treatment failures
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
T7 and T10: 7 and 10 minutes after start of treatment application |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
France |
Germany |
Hungary |
Romania |
Serbia |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |