Clinical Evidence

1. CELOX Rapid Post Market Clinical Survey Report.

Assessment of real-world performance of CELOX™ Rapid by emergency physicians and trained emergency responders 2022

CELOX™ Rapid achieved hemostasis after the first application in 100% of cases carried out by respondents including ER physicians, medics, nurses, and other emergency personnel.

This sub-analysis from a larger CELOX™ 292 study covered 84 cases involving single or multiple wounds ranging from cutting/piercing and blunt trauma to gunshots and road traffic accidents – 90% of which were described as involving ‘moderate to severe bleeding’, 21% of which were on anticoagulation therapy.

Key Findings

• 100% success rate, 84/84 cases achieved haemostasis after the first application using CELOX™ Rapid – even those involving the most severe bleeding cases
• No adverse events reported when using CELOX™ Rapid
• All respondents across the sub-analysis rated CELOX™ Rapid ‘good’ or ‘excellent’
• There were no adverse events recorded

CELOX RAPID PMCF.

2. CELOX Clinical Survey Report

Assessment of real world performance of Celox ^TM Haemostat Device Family by trained emergency responders in 2022

CELOX^TM Haemostat Devices achieved haemostasis after the first application in 99.3% of cases carried out by respondents including ER physicians, medics, nurses and other emergency personnel.

POST MARKET CLINICAL FOLLOW UP EVALUATIONS

The study covered 292 cases involving single or multiple wounds ranging from cutting / piercing and blunt trauma to gunshots and RTAs – 85% of which were described as involving ‘moderate to severe bleeding’.

There were no adverse events for any of the products including those used to treat patients on anticoagulation therapy.

Key Findings

• 99.3% success rate, 290/292 cases achieved haemostasis after the first application – even those involving the most severe bleeding cases
• 100% success rate in cases using CELOX^TM Rapid, the most used product
• 100% success rate on safety: no adverse events reported when using any of the products
• 99% of respondents across the whole study rated the CELOX^TM family of Haemostat Devices ‘good’ or ‘excellent.

CELOX PMCF

3. Winstanley M, Smith JE, Wright C. Catastrophic haemorrhage in military major trauma patients: a retrospective database analysis of haemostatic agents used on the battlefield. J R Army Med Corps. 2019 Dec;165(6):405-409. doi: 10.1136/ jramc-2018-001031. Epub 2018 Oct 3. PMID: 30287682.

Summary: Retrospective database analysis of haemostatic agents used on the battlefield, drawn from the UK Joint Theatre Trauma Registry from 2003 to 2014 during combat operations in Iraq and Afghanistan. Data included patient demographics, the use of haemostatic dressings, New Injury Severity Score (NISS) and patient outcome. Of 3,792 cases, a haemostatic dressing was applied in 317 (either CELOX, HemCon or QuikClot). When comparing patients who had a haemostatic dressing applied versus no haemostatic agent, there was a 7% improvement in survival. The paper also concluded that CELOX was the only individual haemostatic dressing that was associated with a statistically significant improvement in survival.

FOCUS: HAEMORRHAGE CONTROL; INCREASED SURVIVAL – MILITARY

4. Hatamabadi HR, Asayesh Zarchi F, Kariman H, Arhami Dolatabadi A, Tabatabaey A, Amini A. CELOX-coated gauze for the treatment of civilian penetrating trauma: a randomized clinical trial. Trauma Mon. 2015 Feb;20(1):e23862. doi: 10.5812/ traumamon.23862. Epub 2015 Jan 20. PMID: 25825701; PMCID: PMC4362036.

Summary: Randomised clinical trial using CELOX Gauze to treat civilian penetrating trauma in an Iranian hospital ER Department against a control group treated with simple pressure dressings (n= 80 in each group, 160 in total). Examined the role of CELOX in cases including stab wounds with knives and glass and motor vehicle collisions. The time for achievement of haemostasis and the amount of bleeding were recorded. Data were analysed using SPSS Version 21 and Sta ta 13. A P value of less than 0.05 was considered statistically significant. Haemostasis was achieved within 5 minutes in 32.5% of the control group and 51.3% of the intervention group. Using CELOX Gauze significantly reduced the time to haemostasis (P = 0.01) and blood loss was significantly lower in the CELOX group compared t o the controls (P < 0.05). Conclusion: CELOX Gauze achieved haemostasis in penetrating limb trauma considerably faster than conventional pressure bandages.

FOCUS: SPEED OF HAEMOSTASIS IN PENETRATING LIMB TRAUMA

5. Pozza M, Millner RW. CELOX (chitosan) for haemostasis in massive traumatic bleeding: experience in Afghanistan. Eur J Emerg Med. 2011 Feb;18(1):31-3. doi: 10.1097/MEJ.0b013e32833a5ee4. PMID: 20461007.

Summary: Field study illustrating effectiveness of CELOX^TM Granules in treating 21 soldiers in Afghanistan suffering with gunshot wounds, mainly in limbs: prior to CELOX^TM Applicator availability in the field, so teams improvised using plastic syringes with the ends cut off to compact the CELOX^TM deep inside penetrating wounds, leading to quick haemostasis with stable clots. In 18 patients, haemostasis was obtained in less than one minute, while for three patients whose arterial haemorrhage was massive, further applications were necessary. Once haemostasis had been achieved with the formation of the coagulum, compressive medication was applied. For 15 patients with wounds to the limbs, once haemostasis had been obtained, the tourniquet was removed. In all cases, the haemorrhage was controlled. No patient reported pain during or after the administering of CELOX^TM and no changes to the tissue surrounding the injuries were noted. The CELOX^TM was easily irrigated out after definitive treatment. Conclusion: CELOX^TM seemed completely safe and had not shown significant side effects.

FOCUS: RAPID HAEMOSTASIS; STABLE CLOTS; NO APPARENT SIDE EFFECTS; EASY REMOVAL AFTER TREATMENT – MILITARY

6. Tan ECTH, Bleeker CP.: Field experience with a chitosan-based hemostatic dressing. MCI Forum 3(4): 11-15, 2011. (Clinical)

Summary: Field experience of military trauma surgeon working as part of a helicopter-based Dutch medical team. Involved three patients treated while stationed at Volkel Airbase (working alongside Dutch ambulance service) and four during deployment in Afghanistan. Injuries resulted from a severe motor accident, bomb and gunshot wounds. Indication in six patients was traumatic bleeding, and one post-surgical bleeding. After applying the chitosan gauze (described as easy to use and simple to apply), manual pressure was applied for about five minutes and then covered with an occlusive bandage. Cases were purely observational and without long-term follow-up, but the team concluded that CELOX was as easy to use as a gauze bandage and that such dressings should be available to every military nurse and medic in the chain of care – as well as carried by every soldier going into combat.

FOCUS: HAEMOSTASIS; EASE OF APPLICATION – MILITARY / TRAUMA

7. Bar J, David A, Khader T, Mulcare M, Tedeschi C. Assessing Coagulation by Rotational Thromboelastometry (ROTEM) in Rivaroxaban-Anticoagulated Blood Using Hemostatic Agents. Prehosp Disaster Med. 2017 Oct;32(5):580-587. doi: 10.1017/S1049023X17006641. Epub 2017 Jun 19. PMID: 28625215.

Summary: Analysis of human blood samples taken from eight adult patients taking the increasingly common anticoagulant Rivaroxaban and presenting at two US Emergency Departments. Using Rotational Thromboelastometry (ROTEM), study analysed Clotting Time (CT), Clot Formation Time (CFT) and Maximum Clot Firmness (MCF). Of samples treated with a chitosan-based agent, six (75.0%) showed reductions in CT, three (37.5%) showed reductions in CFT, and five (62.5%) showed increases in MCF. Study concludes that chitosan-based haemostatic agents may be effective at improving coagulation in such patients, mainly regarding CT and CTF.

FOCUS: IMPROVED CLOTTING AND CLOT FORMATION IN PATIENTS TAKING RIVAROXABAN

8. Kozen BG, Kircher SJ, Henao J, Godinez FS, Johnson AS. An alternative hemostatic dressing: comparison of CELOX^TM, HemCon, and QuikClot. Acad Emerg Med. 2008 Jan;15(1):74-81. doi: 10.1111/j.1553-2712.2007.00009.x. PMID: 18211317.

Summary: In vivo porcine study of 48 swine (four treatment groups, 12 in each) to compare the performance of SG and combat gauze dressings, CELOX^TM (CX), HemCon (HC) and QuikClot (QC). Each agent was applied with 5 minutes of manual pressure followed by a standard field compression dressing. CX reduced rebleeding to 0% (p < 0.001), HC to 33% (95% CI = 19.7% to 46.3%, p = 0.038), and QC to 8% (95% CI = 3.3% to 15.7%, p = 0.001), compared to 83% (95% CI = 72.4% to 93.6%) for SD. CX improved survival to 100% compared to SD at 50% (95% CI = 35.9% to 64.2%, p = 0.018). Survival for HC (67%) (95% CI = 53.7% to 80.3%) and QC (92%; 95% CI = 84.3% to 99.7%) did not differ from SD. CELOX was the only treatment to reduce rebleeding to 0% and improve survival by 100%.

FOCUS: IMPROVED HAEMORRHAGE CONTROL; IMPROVED SURVIVAL

9. GS Arul, DM Bowley, S DiRusso. The Use of CELOX™ Gauze as an Adjunct to Pelvic Packing in Otherwise Uncontrollable Pelvic Haemorrhage Secondary to Penetrating Trauma.

Summary: Haemorrhage from severe pelvic fractures can be associated with significant mortality. Modern civilian trauma centres may manage these injuries with a combination of external pelvic fixation, extra-peritoneal packing and/or selective angiography; however, military patterns of wounding are different and deployed medical facilities may be resource constrained. We report two successful instances of pelvic packing using chitosan impregnated gauze (Celox™) when conventional surgical attempts at vascular control had failed. We conclude that pelvic packing should be considered early in patients with military pelvic trauma and major haemorrhage, as part of damage control surgery and that Celox™ gauze may be a useful adjunct. In our cases, the Celox gauze was easily removed after 24-48 hours without significant bowel adhesions and did not leave a residual phlegmon (of exudate or gel) that may predispose to infection.

FOCUS: EFFECTIVENESS OF CELOX^TM IN THE TREATMENT OF BLAST INJURIES – MILITARY

10. Henrich, W, Dückelmann A, Giroud D, Sarr Y. Version 1.1 – 19 May 2022. Retrospective analysis study (n=102) on the use of CELOX PPH GAUZE as a treatment for PPH compared with current standard of care. Retrospective analysis study (n=102). Postpartum Haemorrhage: CELOX™ PPH Gauze retrospective data analysis report (Charité data).

Summary: Assessment of 102 patients with PPH who did not respond to conventional treatments. Primary objective: to control uterine bleeding in PPH with CELOX™ PPH. CELOX™ PPH demonstrated 100% successful haemostasis in all patients with grade 1 and 2 bleeds (up to 2500mls) for all deliveries. CELOX™ PPH demonstrated 95.7% successful haemostasis in all patients with grade 1 to 3 bleeds (up to 8000mls) for vaginal deliveries. Following the introduction of CELOX™ PPH the incidence of hysterectomies was significantly reduced (versus standard of care) by 77.8%

FOCUS: USE OF CELOX^TM PPH EFFECTIVENESS VS CURRENT PPH STANDARD OF CARE

11. Dueckelmann AM, Hinkson L, Nonnenmacher A, Siedentopf JP, Schoenborn I, Weizsaecker K, Kaufner L, Henrich W, Braun T. Eur J Obstet Gynecol Reprod Biol. 2019; 240:151-155. Retrospective cohort study (n=78) comparing outcomes in PPH management using CELOX PPH Gauze versus balloon tamponade. Uterine packing with CELOX™ PPH compared to balloon tamponade for managing postpartum haemorrhage.

Summary: Retrospective cohort study (n=78). Assessment of the effectiveness and safety of CELOX™ PPH versus balloon tamponade for managing severe PPH. CELOX™ PPH is an excellent treatment for severe PPH and is at least equivalent to the balloon tamponade. Following the introduction of CELOX™ PPH the incidence of hysterectomies (versus standard of care) was reduced by 50%. CELOX™ PPH is particularly effective in managing PPH resulting from uterine atony or placenta bed bleeding following vaginal or caesarean section deliveries. CELOX™ PPH is especially beneficial for cases involving lower uterine segment atony, placenta previa bed bleeding, and coagulopathy. No adverse events or treatment-related morbidity were linked to CELOX™ PPH

FOCUS: COMPARISON OF PPH MANAGEMENT – CELOX PPH AND BALLOON TAMPONADE

12. Von Beckerath AK, Maul H, Elmohandes AM, Shaaban M, Habib DM, Nasr A, Abdel-Kawi AF. Am J Obstet Gynecol. 2016; 214(1 Suppl 1):S335. [poster presentation]. Randomised, prospective evaluation (n=61) comparing the effectiveness of CELOX GAUZE with balloon tamponade in patients with PPH. Comparison of CELOX™ PPH and Bakri balloon in management of primary atonic postpartum Haemorrhage.

Summary: Assessment of the effectiveness of intrauterine insertion of CELOX™ PPH in comparison to Bakri balloon. Failure rate which led to peripartum hysterectomies were 9.7% (3/31) in the CELOX™ PPH group compared to 40% (12/30) in the Bakri balloon group. CELOX™ PPH is a potentially effective treatment in the management of atonic PPH. CELOX™ PPH is cost effective and is easy to use compared to the standard balloon therapy.

FOCUS: EFFECTIVENESS OF CELOX^TM GAUZE AND BAKRI BALLOON IN PRIMARY ATONIC POSTPARTUMN HAEMORRHAGE

13. Biele C, Radtke L, Kaufner L, Hinkson L, Braun T, Henrich W, Dückelmann AM. J Perinat Med. 2022; 50(8):1078-1086. Historical, retrospective cohort study evaluation (n=666) comparing the effectiveness of chitosan covered (CELOX^TM PPH) Gauze with balloon tamponade or medical therapy in patients with PPH. Does the use of CELOX™ PPH for postpartum haemorrhage reduce the need for surgical therapy including hysterectomy? A databased historical cohort study. Retrospective cohort study (n=666).

Summary: Assessment of the effectiveness of CELOX™ PPH in comparison with balloon tamponade, and medical therapy only. Groups were compared in terms of therapy success, side-effects, and the primary outcome was the need for surgical measures (e.g., hysterectomy). No significant differences in the need for surgical therapy between groups. CELOX™ PPH group had significantly fewer hysterectomies compared to the balloon tamponade group. Following the introduction of CELOX™ PPH, the incidence of PPH-related hysterectomies was significantly reduced by 77.8%. No adverse events related to CELOX™ PPH. CELOX™ PPH is easy to use and cost-effective compared to alternative devices.

FOCUS:  COMPARISON OF CELOX PPH AND BALLOON TAMPONADE OR MEDICAL THERAPY IN PATIENTS WITH PPH

14. Von Beckerath AK, Maul H, Gebauer G, Abdel-Kawi AF, Rolf N, Saade G, Bader W, Kusnierczak D, Berger R, Kienast C, Kienemund J, Schmid B. Am J Obstet Gynecol. 2016; 214(1 Suppl 1):S269. [poster presentation]. Clinical evaluation (n=98) of chitosan-covered (CELOX PPH) Gauze in patients with PPH. Use of CELOX™ PPH in 98 cases of severe postpartum haemorrhage–a multicenter registry analysis. Multicentre registry analysis study (n=98).

Summary: Assessment of the potential side effects of CELOX™ PPH, and to assess if the use of CELOX™ PPH reduces the rate of postpartum hysterectomies. Women with PPH were treated in accordance to guidelines with the addition of uterine packing using CELOX™ PPH. After the introduction of CELOX™ PPH the rate of postpartum hysterectomies reduced from 0.18% to 0.05% (p=0.0183). No adverse events were observed or reported. CELOX™ PPH is cost-effective and easy to use.

FOCUS: USE OF CELOX^TM PPH IN PATIENTS WITH POSTPARTUMN HAEMORRHAGE

15. Maul H, Steinmacher S, Saade G, Gebauer G, Rolf N, Schmid B. Am J Obstet Gynecol. 2015; 212(1 Suppl 1):S358-S359. [poster presentation]. Clinical evaluation (n=65) of chitosan-covered (CELOX PPH) Gauze in patients with severe PPH (including cases where risk of postpartum hysterectomy is high). Uterine packing with CELOX™ PPH for control of postpartum Haemorrhage (PPH).

Summary: Case study series (n=65). Objective: to compare a 26 month period before and a 38 month period after the introduction of CELOX™ PPH in the treatment of PPH. Women with PPH were treated by uterine packing with CELOX™ PPH through the hysterotomy in caesarean delivery, or transvaginally. CELOX™ PPH is a viable option in the treatment of PPH. After the introduction of CELOX™ PPH postpartum hysterectomies were significantly reduced (p=0.023). CELOX™ PPH can be safely used after both vaginal and caesarean section. No complications related to CELOX™ PPH treatment were observed. The use of CELOX™ PPH is inexpensive.

FOCUS: CONTROL OF POSTPARTUM HAEMORRHAGE; UTERINE PACKING WITH CELOX^TM PPH

16. Maul H, Gebauer G, Rolf N, Saade G, Rezniczek G, Schmid B. Am J Obstet Gynecol. 2014; 210(1 Suppl 1):S281-S282. [poster presentation] . Clinical evaluation (n=35) of chitosan-covered (CELOX™ PPH) gauze in patients with PPH. Uterine packing with CELOX™ PPH for control of postpartum Haemorrhage.

Summary: Case study series (n=35). Objective: to describe 26 months of experience using CELOX™ PPH in the treatment of PPH. Over comparable periods of time (26 months) and similar number of births (n=5498 vs. n=6222) before and after the introduction of CELOX™ PPH there was a significant reduction in the rate of postpartum hysterectomies (p=0.011). CELOX™ PPH is a viable option for the treatment of (severe) PPH. CELOX™ PPH is easy to apply and can be used after both vaginal and caesarean deliveries and requires no special training. CELOX™ PPH is inexpensive compared to other treatment options. No complications related to CELOX™ PPH treatment were observed.

FOCUS: CONTROL OF POSTPARTUM HAEMORRHAGE; CELOX^TM PPH

17. Schmid BC, Rezniczek GA, Rolf N, Saade G, Gebauer G, Maul H.. Am J Obstet Gynecol. 2013; 209(3):225.e1-225.e5. Case studies: use of CELOX™ PPH in patients (n=19) with severe PPH (including cases where risk of postpartum hysterectomy is high). Uterine packing with CELOX™ PPH for control of postpartum Haemorrhage.

Summary: Case study series (n=19). Assessment of the use of CELOX™ PPH in the treatment of PPH. Women with PPH were treated with uterine packing using CELOX™ PPH either through the hysterotomy, in the case of caesarean delivery or transvaginally. In all but one case (18/19) bleeding was halted and no further intervention was required. Over equivalent 18-month periods and with a comparable number of births (3822 vs. 4077) before and after the introduction of CELOX™ PPH, the rate of peripartum hysterectomies was reduced by 75% (p = .044).

FOCUS:  CASE STUDY – CONTROL OF POSTPARTUM HAEMORRHAGE UTERINE PACKING WITH CELOX^TM PPH

18. Carles G, Dabiri C, Mchirgui A, Saoudi EO, Hcini N, Pouget K, Seve B, de Matteis B. J Gynecol Obstet Hum Reprod. 2017; 46(9):693-695. Case studies: use of chitosan (CELOX™ PPH Gauze) in patients with (n=4) life-threatening obstetric bleeding. Uses of CELOX™ PPH for treating different forms of serious obstetrics haemorrhages.

Summary: Case study series (n=4).Four cases where CELOX™ PPH was used to treat severe obstetric haemorrhage. Two chitosan variants, in powder and CELOX™ PPH form, were used*. In all four cases, chitosan effectively resolved the severe obstetric haemorrhage. Treatment with CELOX™ PPH was inexpensive, and required no training

FOCUS:  CASE STUDY – TREATMENT OF LIFE-THREATENING BLEEDING WITH CHITOSAN BASED (CELOX^TM PPH) GAUZE

19. Seidel V, Braun T, Weizsäcker K, Henrich W. Int J Surg Case Rep. 2018; 48:101-103. Case report: use of chitosan-covered (CELOX™ PPH) Gauze in combination with balloon tamponade for management of PPH. Application of CELOX™ PPH in combination with intrauterine balloon tamponade for postpartum Haemorrhage treatment – Case report of a novel “uterine sandwich” approach.

Summary: Case report (n=1). Presentation of a case of PPH where a novel “uterine sandwich” (a combination of CELOX™ PPH and intrauterine balloon tamponade) used to halt blood loss. The novel treatment strategy was effective at stopping further blood loss. The use of the “uterine sandwich” prevented the need for more invasive second stage intervention.

FOCUS: POSTPARTUM HAEMORRHAGE TREATMENT; COMBINATION BALLOON TAMPONADE AND CELOX PPH

20. Schmid BC, Rezniczek GA, Rolf N, Maul H. Am J Obstet Gynecol. 2012; 206(1):e12-e13.Case report: use of haemostatic combat (CELOX™ PPH) Gauze in a severe case of PPH. Postpartum Haemorrhage: use of CELOX™ PPH.

Summary: Case report (n=1). Reporting of a case of PPH where conservative treatment proved ineffective, and CELOX™ PPH was used. Tight uterovaginal packing with CELOX™ PPH was performed in an effort to arrest recurring haemorrhage. CELOX™ PPH achieved haemostasis and remained in place for 36 hours. By achieving haemostasis, CELOX™ PPH prevented a seemingly inevitable hysterectomy. The ease of application and cost-effectiveness of CELOX™ PPH present a promising addition to the treatment options for PPH.

FOCUS: SEVERE CASE OF POSTPARTUM HAEMORRHAGE; USE OF CELOX^TM PPH

21. Wolfgang Henrich, MD, PhD; Anna Du¨ckelmann, MD; Thorsten Braun, MD, PhD;
Larry Hinkson, MBBS, MD, MRCOG, FRCOG. Uterine packing with chitosan-covered tamponade to treat postpartum hemorrhage. American Journal of Obstetrics & Gynecology – Expert Review.

Summary: Postpartum hemorrhage (PPH) causes substantial maternal mortality and morbidity and is responsible for a quarter of all maternal deaths worldwide.1 Conventional use of uterotonics such as oxytocin, prostaglandins, and medications to support coagulation, such as fibrinogen and tranexamic acid, are helpful but may not be sufficient to arrest life-threatening PPH. Blood transfusions, intrauterine balloon tamponade application, invasive techniques, such as compression sutures, and arterial ligation are advanced steps in the management cascade. In extreme cases, a hysterectomy may be necessary to avoid maternal death.

FOCUS: UTERINE PACKING WITH CHITOSAN-SOVERED TAMPONADE; TREATMENT OF POSTPARTUM HAEMORRHAGE