BleedingPhase 2NCT03131336
PeproStat as a Topical Agent Used to Stop Bleeding in Patients Undergoing Surgery
A Phase 2 study testing PeproStat and Saline in people with Bleeding, run by Haemostatix Ltd at 5 sites in 5 countries.
Trial summary
The purpose of this study is to test the effectiveness and safety of a new peptide-based coagulant, PeproStat. The study drug will be applied to patients undergoing liver/soft tissue surgery, vascular surgery or spine surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bleeding
- What is being tested?
- PeproStat and Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 169 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 31 Mar 2017to 11 Oct 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is undergoing a planned open liver/soft tissue surgery, vascular surgery or spine surgery.
- Subjects are able and willing to provide written informed consent to participate in this study.
- Adult males and females ≥18 years of age at screening.
- Willing and able to comply with all protocol requirements including follow-up assessments.
- Male subjects must be willing and able to use adequate contraception from enrollment through to the 30 day follow-up visit.
- Women of childbearing potential (WCBP)C have to use highly effective methods of contraception from enrollment through to the 30 day follow-up visit.
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- Intraoperative:
- 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.
- The subject presents no intraoperative complications, other than bleeding, that may interfere with study assessments as judged by the Investigator.
- The subject presents no contaminated areas of the body, signs of infection or abscess development.
- Total target bleeding site surface area of ≤ 70 cm2, defined within one or two TBSs.
Who cannot join
- Subject is undergoing emergency surgical procedure.
- 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.
- Recipient of an organ transplant.
- Haematologic, biochemistry and coagulation panel thresholds at screening:
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- Haemoglobin ≤ 9.0 g/dL.
- Platelet count ≤100,000/mm3 (≤ 100 x 109/L).
- International Normalized Ratio (INR) > 2.0 or activated Partial Thromboplastin Time (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.
- Severe renal failure.
- Any other disease or condition that may affect normal blood clotting, for example thrombocytopenia, as judged by the Investigator.
- 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.
- Participation in another investigational drug or device research study within 30 days before and after enrolment in the current study.
- Current known or suspected alcohol and/or drug abuse or dependence at the time of screening.
- 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.
- Known HIV, Hepatitis B virus or Hepatitis C Virus infection.
- During the surgery, subject presents severe bleeding where use of a topical haemostat would be inappropriate.
- Anti-platelets/oral anticoagulants treatment:
- Soft tissue/liver and neurosurgery: Subject is taking anti-platelet agents or oral anticoagulants within 7 days of surgery
- Vascular surgery: Subject is taking dual anti-platelet treatment or oral anticoagulants within 7 days of surgery. One anti-platelet agent is allowed perioperatively.
- Heparin treatment:
- Soft tissue/liver and neurosurgery only: Subject is receiving therapeutic doses of heparin perioperatively. Only prophylactic Low Molecular Weight Heparin is allowed.
- Pregnant or breast-feeding subject.
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
Bosnia and Herzegovina1 site
University Clinical Hospital, Bolnicka 25
Sarajevo, 71000
Croatia1 site
University Clinical Hospital Centre "Sestre Milosrdnice", Vinogradska cesta 29
Zagreb, 10000
Poland1 site
Klinika Neurochirurgii Gdanskie Centrum Kliniczne, ul. Dębinki 7
Gdansk, 80-952
Serbia1 site
Clinical centre of Serbia, Clinic for vascular and endovascular surgery, Koste Todorovica Street 8
Belgrade, 11000
About this study
Official title: A Controlled, Randomized, Multi-centre, Double Blind, Phase II Study to Evaluate Efficacy and Safety of Topical PeproStat in Intraoperative Surgical Haemostasis
The purpose of this study is to test the effectiveness and safety of a new peptide-based coagulant, PeproStat. The study drug will be applied to patients undergoing liver/soft tissue surgery, vascular surgery or spine surgery. The speed of action of the new coagulant, that is applied with a gelatin sponge, will be compared to the same sponge but with saline (a commonly used standard of care).
Read the detailed description
PeproStat is a new class of topical haemostatic agent composed of recombinant human albumin (rHA) conjugated with fibrinogen-binding peptides. The conjugate polymerises fibrinogen into a fibrin-like clot without the need for thrombin.
PeproStat is formulated in a liquid, and is soaked into a haemostatic gelatin sponge in the operating theatre, and applied directly to the site of bleeding. The gelatin sponge (Spongostan ) is an approved "passive" haemostat i.e., PeproStat is an adjunct to a passive haemostat.
The study is designed in a 2:1 randomization (verum:placebo) to investigate the efficacy in terms of Time to hemostasis, 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 hemostasis at that site or to the end of the 10-minute assessment period if hemostasis has not yet been achieved.
- Conditions
- Bleeding
- Being tested
- PeproStat, Saline
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PeproStatDrug
Also called PeproStat 2.5 mg/mL, soaked into Spongostan
solution for local application
SalineDrug
Also called Absorbable gelatin sponge (Spongostan) soaked with saline
solution for local application
| Study group | Role | What they receive |
|---|---|---|
| PeproStat | Experimental | PeproStat 2.5mg/mL soaked into haemostatic gelatin sponge, applied to a target bleeding site Receives: Drug: PeproStat |
| Saline | Placebo comparator | Saline soaked into haemostatic gelatin sponge, applied to a target bleeding site Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference in time to hemostasis in minutes when using verum vs placebo
Efficacy in terms of Time to hemostasis, mean (mTTH) at the primary target bleed site (TBS),measured in minutes 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.
Measured: 10 minutes after application
Secondary outcomes (28)
Percentage of subjects achieving hemostasis at 1 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Percentage of subjects achieving haemostasis within 1 minute from application of treatment
Measured: 1 minute after start of treatment
Percentage of subjects achieving hemostasis at 2 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Percentage of subjects achieving haemostasis within 2 minutes from application of treatment
Measured: 2 minutes after start of treatment
Percentage of subjects achieving hemostasis at 3 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Percentage of subjects achieving haemostasis within 3 minutes from application of treatment
Measured: 3 minutes after start of treatment
Percentage of subjects achieving hemostasis at 5 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Percentage of subjects achieving haemostasis within 5 minutes from application of treatment
Measured: 5 minutes after start of treatment
Percentage of subjects achieving hemostasis at 7 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Percentage of subjects achieving haemostasis within 7 minutes from application of treatment
Measured: 7 minutes after start of treatment
Percentage of subjects achieving hemostasis at 10 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Percentage of subjects achieving haemostasis within 10 minutes from application of treatment
Measured: 10 minutes after start of treatment
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
Median time for haemostasis to be achieved
Measured: 10 minutes after start of treatment
Number/rate of subjects who do not achieve hemostasis within 10 min
Number/rate of subjects who do not achieve hemostasis within 10 min
Measured: 10 minutes after start of treatment
Number of sponges applied at Target Bleeding Site (TBS)
Number of sponges used at TBS, 1 or 2
Measured: Counted on Day of surgery
Dose of PeproStat determined by number and size (if cut to size) of PeproStat soaked sponges applied at TBS
Dose of PeproStat determined by number and size (if cut to size) of PeproStat soaked sponges applied at TBS
Measured: Measured on day of surgery
Number/rate of treatment failures
Number of participants not achieving haemostasis within 10 minutes at primary, secondary or both TBS's
Measured: 10 minutes after start of treatment
Use of alternative haemostatic agents at the TBS
Number of participants requiring use of other haemostats at the TBS
Measured: Documented on the day of surgery
Investigator assessment of efficacy to obtain haemostasis
Investigator's assessment of the efficacy of the treatment with a score of 1-5, where 5 is very effective
Measured: Documented on the day of surgery
Investigator assessment ease of use of study treatment
Investigator assessment ease of use of study treatment with a score of 1-5, where 5 is very effective
Measured: Documented on the day of surgery
Adverse Events
Number of 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
Measured: Measured from the point of consent to Day 30
Heparin usage
Number of participants with Heparin usage
Measured: Measured from the point of consent to Day 30
Antiplatelet usage
Number of participants with Antiplatelet usage
Measured: Measured from the point of consent to Day 30
Laboratory safety parameters
Changes in Laboratory safety parameters at day 5 vs. screening
Measured: Measured at Day 5
Laboratory safety parameters
Laboratory safety parameters at day 30 vs. screening
Measured: Measured at screening, Day 30
Immunogenicity testing
Immunogenicity testing
Measured: Measured at screening and Day 30
Vital signs
Changes in vital signs
Measured: Measured before surgery vs. screening
Vital signs
Changes in vital signs
Measured: Measured during surgery (before treatment) vs. screening
Vital signs
Changes in vital signs
Measured: Measured during surgery (15 minutes after treatment) vs. screening
Vital signs
Changes in vital signs
Measured: Measured at 4 hours after surgery vs. screening
Vital signs
Changes in vital signs
Measured: Measured at 8 hours after surgery vs. screening
Vital signs
Changes in vital signs
Measured: Measured at 16 hours after surgery vs. screening
12-lead electrocardiogram
Abnormalities in 12-lead electrocardiogram
Measured: measured at Day 5
12-lead electrocardiogram
Abnormalities in 12-lead electrocardiogram
Measured: measured at Day 30 (if medically indicated)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2017
- Study start31 Mar 2017
- Primary completion23 Aug 2017
- Study completion11 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BleedingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, interventional, randomized, controlled, double-blind, parallel group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haemostatix Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Hayes, Principal investigator, Addenbrookes NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03131336
- Sponsor's protocol ID
- HX-02-PEP
- Status last verified
- Feb 2018
- First submitted
- 27 Mar 2017
- Last updated
- 27 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled, Randomized, Multi-centre, Double Blind, Phase II Study to Evaluate Efficacy and Safety of Topical PeproStat in Intraoperative Surgical Haemostasis
- ClinicalTrials.gov ID
- NCT03131336
- Acronym / sponsor ID
- HX-02-PEP
- Conditions
- Bleeding
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 169 participants (actual)
- Lead sponsor
- Haemostatix LtdIndustry (pharma, biotech, devices)
- Study start
- 31 Mar 2017 (actual)
- Primary completion
- 23 Aug 2017 (actual)
- Study completion
- 11 Oct 2017 (actual)
- First posted
- 27 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the effectiveness and safety of a new peptide-based coagulant, PeproStat. The study drug will be applied to patients undergoing liver/soft tissue surgery, vascular surgery or spine surgery. The speed of action of the new coagulant, that is applied with a gelatin sponge, will be compared to the same sponge but with saline (a commonly used standard of care).
Detailed description
PeproStat is a new class of topical haemostatic agent composed of recombinant human albumin (rHA) conjugated with fibrinogen-binding peptides. The conjugate polymerises fibrinogen into a fibrin-like clot without the need for thrombin.
PeproStat is formulated in a liquid, and is soaked into a haemostatic gelatin sponge in the operating theatre, and applied directly to the site of bleeding. The gelatin sponge (Spongostan ) is an approved "passive" haemostat i.e., PeproStat is an adjunct to a passive haemostat.
The study is designed in a 2:1 randomization (verum:placebo) to investigate the efficacy in terms of Time to hemostasis, 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 hemostasis at that site or to the end of the 10-minute assessment period if hemostasis has not yet been achieved.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Prospective, interventional, randomized, controlled, double-blind, parallel group
| Arm | Type | Receives |
|---|---|---|
| PeproStat | Experimental | Drug: PeproStatPeproStat 2.5mg/mL soaked into haemostatic gelatin sponge, applied to a target bleeding site |
| Saline | Placebo comparator | Drug: SalineSaline soaked into haemostatic gelatin sponge, applied to a target bleeding site |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subject is undergoing a planned open liver/soft tissue surgery, vascular surgery or spine surgery.
- Subjects are able and willing to provide written informed consent to participate in this study.
- Adult males and females ≥18 years of age at screening.
- Willing and able to comply with all protocol requirements including follow-up assessments.
- Male subjects must be willing and able to use adequate contraception from enrollment through to the 30 day follow-up visit.
Key exclusion criteria (25 listed)
- Subject is undergoing emergency surgical procedure.
- Use of study treatment and sponge in
- Recipient of an organ transplant.
- Haematologic, biochemistry and coagulation panel thresholds at screening:
- Severe renal failure.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PeproStatAlso: PeproStat 2.5 mg/mL, soaked into Spongostansolution for local application | Drug | PeproStat |
| SalineAlso: Absorbable gelatin sponge (Spongostan) soaked with salinesolution for local application | Drug | Saline |
Primary outcome
The difference in time to hemostasis in minutes when using verum vs placebo
Time frame: 10 minutes after application
Efficacy in terms of Time to hemostasis, mean (mTTH) at the primary target bleed site (TBS),measured in minutes 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.
28 secondary outcomes
Percentage of subjects achieving hemostasis at 1 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Time frame: 1 minute after start of treatment
Percentage of subjects achieving hemostasis at 2 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Time frame: 2 minutes after start of treatment
Percentage of subjects achieving hemostasis at 3 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Time frame: 3 minutes after start of treatment
Percentage of subjects achieving hemostasis at 5 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Time frame: 5 minutes after start of treatment
Percentage of subjects achieving hemostasis at 7 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Time frame: 7 minutes after start of treatment
Percentage of subjects achieving hemostasis at 10 min haemostasis in adult subjects undergoing open liver/soft tissue, vascular and spine surgery using descriptive statistics
Time frame: 10 minutes after start of treatment
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
Time frame: 10 minutes after start of treatment
Number/rate of subjects who do not achieve hemostasis within 10 min
Time frame: 10 minutes after start of treatment
Number of sponges applied at Target Bleeding Site (TBS)
Time frame: Counted on Day of surgery
Dose of PeproStat determined by number and size (if cut to size) of PeproStat soaked sponges applied at TBS
Time frame: Measured on day of surgery
Number/rate of treatment failures
Time frame: 10 minutes after start of treatment
Use of alternative haemostatic agents at the TBS
Time frame: Documented on the day of surgery
Investigator assessment of efficacy to obtain haemostasis
Time frame: Documented on the day of surgery
Investigator assessment ease of use of study treatment
Time frame: Documented on the day of surgery
Adverse Events
Time frame: Measured from the point of consent to Day 30
Heparin usage
Time frame: Measured from the point of consent to Day 30
Antiplatelet usage
Time frame: Measured from the point of consent to Day 30
Laboratory safety parameters
Time frame: Measured at Day 5
Laboratory safety parameters
Time frame: Measured at screening, Day 30
Immunogenicity testing
Time frame: Measured at screening and Day 30
Vital signs
Time frame: Measured before surgery vs. screening
Vital signs
Time frame: Measured during surgery (before treatment) vs. screening
Vital signs
Time frame: Measured during surgery (15 minutes after treatment) vs. screening
Vital signs
Time frame: Measured at 4 hours after surgery vs. screening
Vital signs
Time frame: Measured at 8 hours after surgery vs. screening
Vital signs
Time frame: Measured at 16 hours after surgery vs. screening
12-lead electrocardiogram
Time frame: measured at Day 5
12-lead electrocardiogram
Time frame: measured at Day 30 (if medically indicated)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Hayes principal investigator
Addenbrookes NHS Trust
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PeproStat and Saline in people with Bleeding, run by Haemostatix Ltd at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Bosnia and Herzegovina, Croatia, Poland, Serbia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference in time to hemostasis in minutes when using verum vs placebo (time frame: 10 minutes after application). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2018.