RD2 Ver.02 for Anal Fistulas

Recruiting at 9 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RD2 Ver.02, an autologous blood clot product, to determine its safety and effectiveness for people with anal fistulas, which are abnormal connections between the anus and surrounding skin. Researchers aim to discover if RD2 Ver.02 can heal these fistulas more effectively than the standard saline approach. Participants will be randomly assigned to two groups: one will receive the RD2 Ver.02 treatment, and the other will receive a saline solution. This trial may suit individuals with a transsphincteric or long intersphincteric anal fistula longer than 1.5 cm and who have had a seton (a surgical thread) in place for at least a month. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance future treatment options.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using a product made from a patient's own blood, such as RD2 Ver.02, to treat anal fistulas is generally safe. Past studies found this treatment practical and safe, with a good healing rate. Patients who used RD2 Ver.02 typically tolerated it well, with few complications. These findings suggest that RD2 Ver.02 is a promising and safe option for treating anal fistulas. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for anal fistulas, which often involves surgical procedures like fistulotomy or advancement flap surgery, RD2 Ver.02 offers a unique approach by being applied directly to the fistula tract. This treatment utilizes a novel delivery method, potentially enhancing healing by directly targeting the affected area. Researchers are excited about RD2 Ver.02 because it could lead to more effective healing with fewer complications compared to traditional surgical options, providing relief to patients with less invasive intervention.

What evidence suggests that RD2 Ver.02 might be an effective treatment for anal fistulas?

Research has shown that RD2 Ver.02, a treatment derived from the patient's own blood, holds promise for healing anal fistulas. In this trial, participants in the treatment arm will receive RD2 Ver.02, which earlier studies found to be safe and effective, with a good healing rate for this condition. The treatment forms a clot inside the fistula using the patient's blood, promoting healing. This method aims to reduce complications and recurrence of the fistula. Early results suggest fewer infections around the rectum with RD2 Ver.02 compared to other treatments. Overall, RD2 Ver.02 appears to be a promising option for treating anal fistulas. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10901226/

A Prospective, Single-Arm Study to Evaluate the Safety and ... Treatment with an autologous blood clot product in perianal fistular disease was found to be feasible and safe, with an acceptable healing rate.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05641844?term=AREA%5BBasicSearch%5D(clot%2002)&rank=1

A Double Blind, Randomized Controlled Study, Evaluating ... Incidence of perirectal infection by 6 months in anal fistulas treated with RD2 Ver. 02 compared to control. Infection assessment of the anal fistula, 6 months ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05641844

Study Details | NCT05641844 | A Double Blind, ... 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38149981/

A Prospective, Single-Arm Study to Evaluate the Safety and ... Conclusions: Treatment with an autologous blood clot product in perianal fistular disease was found to be feasible and safe, with an acceptable ...

5. link.springer.com link.springer.com/article/10.1007/s10151-024-02973-9

Efficacy and safety of RD2 Ver.02, a whole blood clot ... Patients with PNS underwent a minimally invasive trephine procedure under local anesthesia followed by RD2 Ver.02 instillation into the cavity.