RD2 Ver.02 for Anal Fistulas

Recruiting at 8 trial locations

Overseen By Alon Kushnir

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: RedDress Ltd.

Must not be taking: Systemic steroids

Disqualifiers: Pregnancy, Active infection, Crohn's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day (procedure)

110 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude those currently receiving systemic steroids or investigational drugs. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment RD2 Ver.02 for anal fistulas?

Research shows that using autologous platelet-rich plasma (PRP), which is similar to the components in RD2 Ver.02, can be effective in treating anal fistulas. Studies have found that PRP helps heal these fistulas by promoting tissue repair and reducing inflammation. ^{1 2 3 4 5}

Is the Autologous Blood Clot Product safe for use in humans?

The preparation of autologous fibrin glue (a type of blood clot product) from plasma has been shown to be safe in a pilot study involving healthy donors. ^{6 7 8 9 10}

How is the RD2 Ver.02 treatment for anal fistulas different from other treatments?

RD2 Ver.02 is unique because it uses the patient's own blood to create a clot that is applied directly to the fistula, promoting healing from within. This approach is different from traditional treatments as it leverages the body's natural healing processes without relying on external materials or medications. ^{8 11 12 13 14}

What is the purpose of this trial?

The goal of this clinical trial is to assesses the safety of autologous RD2 Ver.02 as compared to a control for managing transsphincteric and intersphinsteric anal fistulas. The main questions it aims to answer are: Assess the safety and efficacy of RD2 Ver.02 in anal fistula application, compared to control. Complication rate by 6 months of anal fistula treatment with RD2 Ver.02 compared to control. Recurrence of anal fistula at 12 months post-treatment Incidence of perirectal infection by 6 months in anal fistulas treated with RD2 Ver.02 compared to control. Patients will be randomized in to 2 arms. For all patients, blood will be drawn to ensure the blinding of the patients, the fistula will be evaluated and debrided, and then the internal fistula opening will be suture-closed, and a water leak test will be performed to ensure sealing. Following the water leak test, In the treatment arm, the patient's own coagulating blood will be applied into the entire fistula tract, allowing it to clot and serve as a provisional matrix inside the fistula tract. In the control arm, the blood sample will be discarded and saline will be applied to the fistula tract.

Eligibility Criteria

This trial is for adults over 18 with a specific type of anal fistula, who have had a seton in place for at least one month. They should not be candidates for or willing to undergo invasive surgical procedures and must have confirmed their condition with an MRI. Participants must use contraception if they can conceive.

Inclusion Criteria

I am using or willing to use approved birth control methods for 6 months after the study.

I have a long anal fistula and have had a seton for over a month.

I prefer minimally invasive treatment for my anal fistula over surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo debridement of the fistula tract, suturing of the internal opening, and a water leak test. In the treatment arm, RD2 Ver.02 is applied to the fistula tract; in the control arm, saline is applied.

1 day (procedure)

1 visit (in-person, operating room)

Follow-up

Participants are monitored for safety and efficacy, including assessment of fistula healing and adverse events.

12 months

Regular visits (frequency not specified)

Treatment Details

Interventions

• RD2 Ver.02

Trial Overview The study tests RD2 Ver.02, using the patient's own blood to create a clot as treatment, against saline application in managing anal fistulas. It's randomized and double-blind, meaning neither patients nor doctors know who gets which treatment until after the results are collected.

Participant Groups

Group I: Treatment arm Experimental Treatment 2 Interventions

Subjects will undergo debridement of the fistula tract and suturing of internal opening, followed by a. water leak test. RD2 Ver.02 will be applied to the fistula tract in the operating room.

Group II: Control arm Experimental Treatment 1 Intervention

Subjects will undergo debridement of the fistula tract and suturing of internal opening, followed by a. water leak test. Saline will be applied to the fistula tract in the operating room.

RD2 Ver.02 is already approved in United States for the following indications:

Approved in United States as RD2-Ver.02 for:

• Transsphincteric and intersphincteric anal fistulas

Who Is Running the Clinical Trial?

RedDress Ltd.

Lead Sponsor

Trials

7

Recruited

790+

Findings from Research

Platelet-rich plasma (PRP) treatment for anal fistula showed a pooled cure rate of 65% based on a meta-analysis of 9 studies involving 289 patients, indicating its efficacy.

The recurrence rate of anal fistula after PRP treatment was found to be low at 12%, suggesting that PRP is a safe option for patients and warrants further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of platelet-rich plasma therapy for anal fistula. Luo, Q., Zhou, P., Chang, S.[2022]

The use of autologous fibrin gel rich in platelet growth factors (Vivostat PRF®) for treating complex perianal fistulas showed a success rate of 62% among 23 patients, indicating its effectiveness in promoting healing.

Importantly, no patients experienced incontinence as a result of the treatment, and only two reported a decline in quality of life, highlighting the safety of this technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using autologous platelet-rich plasma for the treatment of complex fistulas. Moreno-Serrano, A., García-Díaz, JJ., Ferrer-Márquez, M., et al.[2017]

Platelet-rich plasma (PRP) treatment for anal fistula demonstrated a high overall cure rate of 72.11% across 14 studies involving 514 patients, with even better results (83.12% cure rate) when combined with other treatments.

PRP treatment showed a low recurrence rate of 14.84% and a low adverse event rate of 6.31%, indicating it is a safe and effective option for patients with anal fistula.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet-rich plasma in the treatment of anal fistula: a systematic review and meta-analysis. Wang, Y., Rao, Q., Ma, Y., et al.[2023]

The study evaluated the use of autologous platelet-rich plasma (PRP) and platelet-rich fibrin glue (PRFG) in treating complex anal fistulas that had not healed after multiple surgeries, involving 10 patients over a follow-up period of 10 to 84 months.

The treatment was found to be safe, with no complications reported, and resulted in the cessation of anal fistula leakage in 6 out of 10 patients, suggesting that PRP and PRFG can enhance healing rates when used alongside traditional surgical methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous platelet-rich-plasma injection and platelet-rich fibrin glue interposition for treatment of anal fistula resistant to surgery. Abdollahi, A., Emadi, E., Hamidi Alamdari, D.[2023]

In a study of 56 patients with high cryptogenic fistulae-in-ano, treatment with autologous platelet-rich growth factor (PRP) showed a healing rate of 71%, compared to 58.3% for commercial fibrin glue, indicating PRP may be more effective.

PRP treatment resulted in lower pain scores and improved quality of life without adverse effects on continence, making it a safe and potentially more beneficial option for managing anal fistulae.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet-rich plasma (PRP) versus fibrin glue in cryptogenic fistula-in-ano: a phase III single-center, randomized, double-blind trial. de la Portilla, F., Muñoz-Cruzado, MVD., Maestre, MV., et al.[2020]

In a Phase 4 study involving 31 adult patients, re-exposure to recombinant human thrombin (rThrombin) was found to be safe, with no patients developing antibodies against the treatment, indicating low immunogenicity.

The most common adverse events reported were mild to moderate, including procedural pain, constipation, and nausea, all deemed unrelated to the rThrombin treatment, suggesting that it can be safely used in patients with prior exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of re-exposure to recombinant human thrombin in surgical hemostasis. Singla, NK., Gasparis, AP., Ballard, JL., et al.[2016]

Recombinant human thrombin (rThrombin) was found to be well tolerated in 583 patients across various surgical procedures, with adverse events similar to typical postoperative complications, indicating its safety as a topical hemostatic agent.

Only 0.9% of patients developed antibodies to rThrombin, and these antibodies did not affect the activity of native human thrombin, suggesting that immunogenicity is low and does not compromise the treatment's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity observations pooled from eight clinical trials of recombinant human thrombin. Ballard, JL., Weaver, FA., Singla, NK., et al.[2016]

A pilot study confirmed that apheresis is a safe method for collecting 2 units of red blood cells and 400 ml of plasma from healthy donors for autologous blood transfusion.

The collected plasma can be effectively used to produce autologous fresh frozen plasma (Auto-FFP) and autologous fibrin glue (Auto-FG), which helps reduce the need for allogeneic fibrin glue in surgical patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large volume apheresis of autologous plasma and preparation of autologous fibrin glue from the plasma. Komatsu, F., Yoshida, S.[2019]

Homologous blood transfusions carry significant risks, including the potential for transfusion-transmitted hepatitis and immunologic effects, making autologous transfusion methods like normovolemic hemodilution (NHD) a safer alternative.

NHD, along with other autologous methods such as intraoperative blood salvage and preoperative blood donation, offers effective blood-saving measures that are not only cost-effective but also legally supported for patient use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The present possibilities for routine use of blood-saving measures from the anesthesiologic point of view--theoretical basis and clinical practice. I. Potential risks of homologous transfusion; normovolemic hemodilution]. Singbartl, G., Schleinzer, W.[2017]

Recombinant human thrombin (rThrombin) was found to be well tolerated in a pooled analysis of 10 clinical trials involving 644 patients, with adverse events primarily being mild to moderate and not leading to any discontinuations from the studies.

Only 0.8% of patients developed antibodies to rThrombin by day 29, and these antibodies did not neutralize the activity of native human thrombin, indicating a favorable safety profile for its use as a topical hemostatic agent in various surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of recombinant human thrombin: a pooled analysis of results from 10 clinical trials. Singla, NK., Foster, KN., Alexander, WA., et al.[2022]

A new system for producing autologous platelet-rich plasma and red blood cell concentrates was successfully used in 15 cardiac surgeries, eliminating the need for homologous blood products.

This approach not only reduced costs associated with blood transfusions but also minimized the risk of infections, as no complications from homologous blood were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new technique for hemodilution, preparation of autologous platelet-rich plasma and intraoperative blood salvage in cardiac surgery. Ferrari, M., Zia, S., Valbonesi, M., et al.[2017]

A new venous-thrombus aspiration and autologous blood reinfusion system was successfully developed and tested using various catheter sizes in a controlled model, demonstrating the ability to aspirate thrombi effectively.

The study found no significant differences in thrombus aspiration volumes or rates between different catheter types, indicating that the system can reliably remove acute venous thrombi regardless of the catheter used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro investigation of a new thrombus aspiration and autologous blood reinfusion system. Li, W., Li, Q., Zhai, S., et al.[2022]

In a pilot study involving 7 patients with serious health issues, the autologous whole blood clot matrix showed a high efficacy rate, achieving complete healing in 78% of chronic wounds treated.

The method was found to be safe, with no systemic adverse events reported, and only one unrelated mechanical trauma noted during the study, indicating a promising approach for chronic wound management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of a Novel Autologous Wound Matrix in the Management of Complicated, Chronic Wounds: A Pilot Study. Kushnir, I., Kushnir, A., Serena, TE., et al.[2017]

The autologous whole blood clot (ACWB) treatment was effective in healing complex wounds, with complete healing observed in 4 out of 5 patients with various hard-to-heal conditions.

ACWB treatment works by forming a fibrin matrix that mimics the extracellular matrix, allowing it to fill deep wound cavities and promote healing safely and efficiently.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Active Coagulation Whole Blood-An Innovative Treatment Strategy for Hard-To-Heal Wounds. Haim, N., Kaufman, JP., Gurevich, M.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Meta-analysis of platelet-rich plasma therapy for anal fistula. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Using autologous platelet-rich plasma for the treatment of complex fistulas. [2017]

3. Germany pubmed.ncbi.nlm.nih.gov

Platelet-rich plasma in the treatment of anal fistula: a systematic review and meta-analysis. [2023]

4. Iran pubmed.ncbi.nlm.nih.gov

Autologous platelet-rich-plasma injection and platelet-rich fibrin glue interposition for treatment of anal fistula resistant to surgery. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Platelet-rich plasma (PRP) versus fibrin glue in cryptogenic fistula-in-ano: a phase III single-center, randomized, double-blind trial. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of re-exposure to recombinant human thrombin in surgical hemostasis. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity observations pooled from eight clinical trials of recombinant human thrombin. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

Large volume apheresis of autologous plasma and preparation of autologous fibrin glue from the plasma. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

[The present possibilities for routine use of blood-saving measures from the anesthesiologic point of view--theoretical basis and clinical practice. I. Potential risks of homologous transfusion; normovolemic hemodilution]. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of recombinant human thrombin: a pooled analysis of results from 10 clinical trials. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

A new technique for hemodilution, preparation of autologous platelet-rich plasma and intraoperative blood salvage in cardiac surgery. [2017]

12. China pubmed.ncbi.nlm.nih.gov

In vitro investigation of a new thrombus aspiration and autologous blood reinfusion system. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of a Novel Autologous Wound Matrix in the Management of Complicated, Chronic Wounds: A Pilot Study. [2017]

14. United States pubmed.ncbi.nlm.nih.gov

The Use of Active Coagulation Whole Blood-An Innovative Treatment Strategy for Hard-To-Heal Wounds. [2023]