E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To achieve haemostasis when bleeding cannot be controlled by conventional methods alone, such as manual pressure, cauterization, or sutures; or are inappropriate. |
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E.1.1.1 | Medical condition in easily understood language |
To stop bleeding when conventional methods alone cannot stop bleeding. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053001 |
E.1.2 | Term | Surgical haemostasis |
E.1.2 | System Organ Class | 100000004865 |
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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 primary objective is to evaluate the efficacy of PeproStat in intraoperative hemostasis in adult subjects who undergo open liver/soft tissue surgery, vascular surgery or spine surgery |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to further investigate the safety of PeproStat |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is undergoing a planned open liver/soft tissue surgery, vascular surgery or spine surgery. 2. Subjects are able and willing to provide written informed consent to participate in this study. 3. Adult males and females ≥18 years of age at screening. 4. Willing and able to comply with all protocol requirements including follow-up assessments. 5. Male subjects must be willing and able to use adequate contraception from enrollment through to the 30 day follow-up visit. 6. Women of childbearing potential (WCBP) have to use highly effective methods of contraception from enrollment through to the 30 day follow-up visit. Such methods include: Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal. Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable or implantable. Intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence 7. The subject presents an identified target bleeding site with mild or moderate bleeding, which conventional surgical techniques are insufficient to control or are inappropriate and would otherwise be a candidate for standard haemostats. 8. The subject presents no intraoperative complications, other than bleeding, that may interfere with study assessments as judged by the Investigator. 9. The subject presents no contaminated areas of the body, signs of infection or abscess development. 10. Total target bleeding site surface area of ≤ 70 cm2, defined within one or two TBSs
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E.4 | Principal exclusion criteria |
1. Subject is undergoing emergency surgical procedure. 2. Use of study treatment and sponge in • Closure of skin incisions as the sponge may interfere with the healing of skin edges. • Intravascular compartments because of the risk of embolization following sponge application. 3. Recipient of an organ transplant. 4. Haematologic, biochemistry and coagulation panel thresholds at screening: • Haemoglobin ≤ 9.0 g/dL. • Platelet count ≤100,000/mm3 (≤ 100 x 109/L). • International Normalized Ratio (INR) > 2.0 or aPTT ratio > 2.0. • Fibrinogen level < 1.5 g/L. • Aspartate Aminotransferase (AST) or Alanine aminotransferase (ALT) ≥ 3 times the upper limit normal range, except for subjects undergoing liver resection surgery where there is no upper limit for these analytes due to the nature of their disease. 5. Severe renal failure. 6. Any other disease or condition that may affect normal blood clotting, for example thrombocytopenia, as judged by the Investigator. 7. A known history of anaphylaxis or allergic reaction to human albumin, PEGylated proteins, yeast or moulds, porcine products or other components in the study medication or sponge. 8. Participation in another investigational drug or device research study within 30 days before and after enrolment in the current study. 9. Current known or suspected alcohol and/or drug abuse or dependence at the time of screening. 10. Any concurrent medical, surgical, or psychiatric condition that may, in the Investigator’s opinion, affect the subject’s willingness or ability to meet all study requirements during the study duration. 11. Known HIV, HBV or HCV infection. 12. During the surgery, subject presents severe bleeding where use of a topical haemostat would be inappropriate. 13. Anti-platelets/oral anticoagulants treatment: a. Soft tissue/liver and neurosurgery: Subject is taking anti-platelet agents or oral anticoagulants within 7 days of surgery. b. Vascular surgery: Subject is taking dual anti-platelet treatment or oral anticoagulants within 7 days of surgery. One anti-platelet agent is allowed perioperatively. 14. Heparin treatment: a. Soft tissue/liver and neurosurgery only: Subject is receiving therapeutic doses of heparin perioperatively. Only prophylactic LMWH is allowed. 15. Pregnant or breast-feeding subject. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the investigation of efficacy in terms of Time to haemostasis, mean (mTTH) at the primary target bleed site (TBS), measured in minutes (min) from the start of treatment application (TxStart) at the TBS to the achievement of haemostasis at that site or to the end of the 10-minute assessment period if haemostasis has not yet been achieved. If haemostasis is not achieved within 10 minutes at the primary TBS, the patient is considered a treatment failure. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints, efficacy: 1. Percentage of subjects achieving hemostasis at 1, 2, 3, 5, 7 & 10 min; 2. Median time to hemostasis in minutes from TxStart to the achievement of hemostasis or to the end of the 10-minute assessment period if hemostasis has not yet been achieved; 3. Number/rate of subjects who do not achieve hemostasis within 10 min; 4. Number and size (if cut to size) of sponges applied at TBS, i.e., 1 or 2 sponges at TBS; 5. Dose of PeproStat determined by number and size of PeproStat soaked sponges applied at TBS; 6. Number/rate of treatment failures: Subjects not having obtained hemostasis within the 10-minute assessment period (primary, secondary and both TBS); 7. Use of alternative hemostatic agents at the TBS; 8. Investigator assessment of efficacy to obtain haemostasis (scale of 1-5, where 5 is very effective); 9. Investigator assessment ease of use of study treatment (score 1 – 5 where 5 is very easy to use).
Secondary endpoints, safety: 10. Adverse events (AEs) including adverse events of special interest: Bleeding at the TBS after 10-minute assessment period during or after surgery (if re-operation is required) and transfusion requirement; 11. Antiplatelet/ heparin usage; 12. Laboratory safety parameters; 13. Immunogenicity testing; 14. Vital signs: heart rate (HR), blood pressure (BP), respiratory rate (RR); arterial oxigenation (pulse oximetry, PO); 15. 12-lead electrocardiogram (ECG). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Saline soaked into Absorbable haemostatic gelatin sponge (Spongostan) |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
Bosnia and Herzegovina |
Croatia |
Germany |
Poland |
Serbia |
Ukraine |
United Kingdom |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |