Scientific Evidence

1. CELOX^TM Rapid maintains haemostasis without re-bleeding

Title: Mechanism of action of rapid-action gauze haemostat.¹

Authors: Hoggarth A, Hardy C, Eason G, Lyon A, Marsden C.

Publication:   Presented at ATACCC, FL, August 2012.

Method: CELOX^TM Rapid haemostatic gauze is designed to stick to wet tissue. Two tests were carried out to evaluate the effectiveness of the ‘wet-stick.’ First, strips of gauze haemostats were pressed on to pork belly and the force to remove was measured, using a tensiometer, after 1, 3 or 20 minutes. Secondly, swine femoral artery injury models were treated and then the models were driven over rough ground for approximately five minutes to simulate a casualty movement, before being examined for evidence of re-bleeding.

Results: The force to remove CELOX Rapid from pork belly was 1.02 N/25mm after one minute and consistent up to the end of test. Other products recorded forces <0.1 N/25mm, below the validated limit of the gauge. In the transport test, CELOX^TM Rapid had zero (0/5) bleeding after transport, whereas QuikClot Combat^® Gauze showed evidence of re-bleeding in three of the five models.

Discussion:

• CELOX^TM Rapid adhered to wet tissue significantly more than other haemostatic gauzes.
• After haemostasis was achieved, CELOX^TM Rapid was able to maintain haemostasis in a model of casualty transport, without re-bleeding.

2. CELOX^TM Rapid reduces blood loss and has a short application time

Title: Chitosan based haemostatic dressing is associated with decreased blood loss in a swine uncontrolled haemorrhage model.²

Authors: Kunio NR, Riha GM, Watson KM, Differding JA, Schreiber MA, Watters JM.

Publication: Am J Surg 2013 May; 205(5):505-510.

Method: The study consisted of a randomised, controlled, blinded trial of lethal femoral arteriotomy injury, utilising thirty-six swine. The injuries were treated with either Standard Gauze, Combat Gauze, or CELOX^TM Rapid Gauze. After packing, there was no further compression applied. Animals were followed for 120 minutes after injury or until death.

Results: All animals survived to study end. Physiologic parameters were similar between groups throughout the study. Dressing success rates were: CELOX^TM Rapid: 12/12; Combat Gauze 10/12; Standard Gauze 10/12 (p=0.14). Post-treatment blood loss for CELOX^TM Rapid (12.8 ml) was significantly reduced compared to Standard Gauze (44.7 ml) or Combat Gauze (31.9 ml) (p=0.05). Packing time was also significantly shorter with CELOX^TM Rapid (37.1 seconds) compared to either Gauze (45.2) or Combat Gauze (43.5) (p=0.01).

Discussion:

• CELOX^TM Rapid had a shorter application time than Combat Gauze or Standard Gauze.
• CELOX^TM Rapid decreased secondary blood loss compared to Combat Gauze and Standard Gauze.
• CELOX^TM Rapid had a trend to higher haemostasis than other dressings tested.³¹

3. CELOX^TM Rapid achieves haemostasis, even without compression

Title: Testing a new gauze haemostat with reduced treatment time.³

Authors: Hoggarth A, Hardy C, Millner R, Lyon A.

Publication: Presented at ATACCC, FL, August 2011.

Method: The test consisted of a lethal 6mm punch arteriotomy to the femoral artery of Yorkshire swine. Treatment was with CELOX^TM Rapid (n=12) or Combat Gauze (8). Haemostasis was assessed after no compression and (where needed) after one-minute compression. Additional tests were carried out with CELOX^TM Rapid and three-minute compression to test equivalence to previous-generation products.

Results: CELOX^TM Rapid had 75% haemostasis with no compression, compared to 38% for Combat Gauze. After one-minute compression, the results were 83% and 50% respectively. Initial haemostasis was sustained to study end. CELOX^TM Rapid was removed intact, with no tissue damage.

Discussion:

• The study deliberately used short treatment time to test the effect of application
  in emergency or high-stress situations.
• CELOX^TM Rapid achieved haemostasis reliably with short compression time or zero compression time.

4. CELOX^TM Rapid is quicker to pack a wound than Combat Gauze

Title: Reduced application time with a rapid packing gauze haemostat.⁴

Authors: Hoggarth A, Hardy C, Eason G, Marsden C.

Publication: Presented at ATACCC, FL, August 2012.

Method: Three different haemostatic gauzes (CELOX^TM Rapid, Chitogauze,® Combat Gauze) were packed into wounds and the pack time measured. This was done first in a simulated wound cavity in pork belly, 10 repeats, then in field tests on a swine femoral artery sever model (n=5 for each product). (Chitogauze not tested in field tests).

Results: Packing times in the laboratory were: CELOX Rapid 12.8 seconds; Combat Gauze 28.3 seconds; ChitoGauze 30.6 seconds. Field packing times were longer: CELOX^TM Rapid 28.8 seconds, Combat Gauze 43.2 seconds.

Discussion:

• CELOX Rapid was faster to pack than the other products in both tests.
• CELOX Rapid is a shorter, denser bandage than the other products (1.5m as opposed to 3.7m).
• The difference in packing time is consistent with the difference in bandage length.

5. CELOX^TM Rapid rapidly stops severe arterial bleeding

Title: Efficacy assessment of CELOX^TM Rapid (CR) gauze to control arterial haemorrhage in normal and coagulopathic swine⁵

Authors: Kheirabadi B.

Publication: Protocol A-17-010-TS1. Data on file 2017.

Method: The efficacy of CELOX^TM Rapid was evaluated in 2 swine with normal blood clotting function and 2 with moderate coagulopathy. The coagulopathic condition was produced by replacing 25% of pigs’ blood volume with Hextend fluid (25% haemodilution) and allowing hypothermia (core temperature 34°-35° C) to occur in the swine prior to arterial injury and haemorrhage.

Results: The CELOX^TM Rapid dressing was an effective haemostat capable of stopping severe arterial bleeding, when applied directly on the injury site and compressed for only 1 minute. CELOX^TM Rapid also appeared to be more adherent to the tissues (i.e. more efficacious) in the presence of blood with normal clotting properties as the blood clot that forms between the dressing and tissues strengthened binding of the chitosan materials to the underlying tissues. It may also be effective in treating haemorrhage in patients with moderate coagulopathy, however, it may require repeated application and longer compression. CELOX Rapid did not shed chitosan particles or leave other residues when was removed from the wound.

6. CELOX^TM Rapid rapidly stops severe arterial bleeding in coagulopathic swine

Title: Efficacy assessment of CELOX^TM Rapid (CR) gauze to control arterial haemorrhage in coagulopathic swine⁶

Authors: Kheirabadi B.

Publication: Protocol A-17-010-TS3. Data on file 2018.

Method: The efficacy of CELOX^TM Rapid was evaluated in 4 swine with acquired coagulopathy. This condition was produced by replacing 25% of circulating blood volume with Hextend fluid (25% haemodilution) and allowing hypothermia (core temperature 34°-35° C) to occur prior to arterial injury and haemorrhage.

Results: The CELOX^TM Rapid dressing was an effective haemostat capable of stopping severe arterial bleeding for a few hours.

7. Statistically significant improved survival with CELOX^TM Gauze

Title: Catastrophic haemorrhage in military major trauma patients: a retrospective database analysis of haemostatic agents used on the battlefield.⁷

Authors: Winstanley M, Smith JE, Wright C

Publication: R Army Med Corps 2018;0:1–5.

Method: A retrospective database review was undertaken, using 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.

Results: Of 3,792 cases, a haemostatic dressing was applied in 317 (either CELOX^TM, Hemcon or QuikClot). When comparing patients who had a haemostatic dressing applied versus no haemostatic agent, there was a 7% improvement in survival. CELOX^TM was the only individual haemostatic dressing that was associated with a statistically significant improvement in survival, which was most apparent in the more severely injured (NISS 36–75).

Discussion:

We have shown an association between use of haemostatic agents and improved survival, mostly in those with more severe injuries, which is particularly evident in those administered CELOX^TM. This supports the continued use of haemostatic agents as part of initial haemorrhage control for patients injured in conflict and suggests that civilian organisations that may need to deal with patients with similar injury patterns should consider their use and implementation.

8. Increased survival and reduced blood loss with CELOX^TM Gauze vs Combat Gauze and ChitoGauze®

Title: Comparison of novel haemostatic gauzes to QuikClot Combat Gauze in a standardised swine model of uncontrolled haemorrhage.⁸

Authors: Rall JM, Cox JM, Conger AG, Cestero RF, Ross JD.

Publications: J Trauma Acute Care Surg 75(2) suppl 2 S150 -156 (2013).

Method: Four haemostatic gauzes (CELOX^TM Gauze 10-foot, Combat Gauze XL, ChitoGauze and CELOX^TM Trauma Gauze) were compared to Combat Gauze in a swine model of groin arterial haemorrhage, with 10 models for each dressing type.

Results: CELOX^TM Gauze achieved 90% survival, while other dressings recorded 50–70%. Blood loss when using Celox Gauze was around half that lost when using Combat Gauze, and the difference was statistically significant after 10 minutes’ treatment. At study end, CELOX^TM Gauze had the lowest observed value for blood loss and highest percentage with haemostasis intact, although these figures were not statistically significant – the study was not powered to show significance. Particles of chitosan were found outside treated vessels, but no foreign material was found inside any vessels, and all products had similar scores for tissue compatibility.

Discussion:

The authors suggest that the larger products (CELOX^TM Gauze 10 foot and Combat Gauze XL) had better results, possibly due to additional tamponade. However, Medtrade internal results on 1.5m and 3m dressings indicate that, for CELOX^TM Gauze, the dressing size does not affect the result.³¹

9. Reduced blood loss and requirement for resuscitation fluids with CELOX Gauze

Title: Advanced haemostatic dressings are not superior to gauze for care-under-fire scenarios.⁹

Authors:         Watters JM, Van PY, Hamilton GJ, Sambasivan C, Differding JA, Schreiber MA.

Publications: J Trauma. 2011 Jun;70(6):1413-9.

Methods: CELOX^TM Gauze was compared to QuikClot Combat Gauze in a model of a wound with no compression applied, the authors arguing that this represents a model of care-under-fire.

Results: CELOX^TM Gauze achieved haemostasis in 6/8 cases, compared with Combat Gauze which achieved haemostasis in 4/8. Standard Gauze achieved higher haemostasis than Celox Gauze, which was explained by the high level of experience of the packer involved. At 30 minutes, CELOX^TM Gauze recorded a significantly shorter time to clot, compared with Standard Gauze and Combat Gauze (p < 0.05). Post-treatment blood loss was lowest for CELOX^TM Gauze 110ml; Standard Gauze 120ml; Combat Gauze 194ml. Requirement for resuscitation fluid given was also lowest for CELOX^TM Gauze 1,170 ml; Combat Gauze 2,000; Standard Gauze 1,825.

Discussion:

In the conference discussion when the study was presented, the author ascribed the performance of Standard Gauze in this model to the level of experience of the packer. No inflammation, necrosis, or deposition of dressing particles in vessel walls were observed. No histologic or ultrastructural differences were found between the study dressings.

References

1. Hoggarth A, et al. Mechanism of action of a rapid-acting gauze hemostat. Poster presentation at ATACCC 2011, Fort Lauderdale, FL (In-vitro).

2. Kunio N, et al. Chitosan based advanced hemostatic dressing is associated with decreased blood loss in swine uncontrolled hemorrhage model. Am J Surg. 2013; 205:505-510 (In-vivo).

3. Hoggarth A, et al. Testing a new gauze hemostat with reduced treatment time. Poster presentation at ATACCC, Ft Lauderdale, August 2011. (In-vitro).

4. Hoggarth A, et al. Reduced application time with a rapid-packing gauze haemostat. Poster presentation at ATACCC 2011, FL (In-vivo).

5. Kheirabadi B. Efficacy assessment of Celox Rapid (CR) gauze to control arterial hemorrhage in normal and coagulopathic swine. Protocol A-17-010-TS1.Data on File 2017 (In-vivo).

6. Kheirabadi B. Efficacy assessment of Celox Rapid (CR) gauze to control arterial hemorrhage in normal and coagulopathic swine. Protocol A-17-010-TS3.Data on File 2018 (In-vivo).

7. 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 2018;0:1-5 (In-vivo).

8. Rall JM, et al. Comparison of novel hemostatic gauzes with QuikClot Combat Gauze in a standardized swine model of uncontrolled haemorrhage. J Trauma Acute Care Surg 75(2) suppl 2 S150 -156 (2013) (In-vivo).

9. Watters JM et al. Advanced hemostatic dressings are not superior to gauze for care-under-fire scenarios. J Trauma. 2011 Jun;70(6):1413-9. (In-vivo).