Hyperbaric Oxygen Therapy for Hemorrhagic Cystitis Post HSCT

NCT04502628 | Unknown DMC

• 1 other identifier: HBOT for HC
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for many malignant or nonmalignant hematological diseases. Hemorrhagic cystitis (HC) is one of the common and major causes of morbidity in patients undergoing allo-HSCT. Its incidence ranges from 7 to 52%, and its manifestations range from painless microscopic hematuria to severe bladder hemorrhage, leading to clot formation within the urinary tract and even renal failure. This complication results in much pain to the patient and increasing treatment cost. Late-onset HC (two weeks after stem cell infusion) has been associated with reactivation of viruses, including cytomegalovirus, polyoma BK and JC viruses, and adenovirus types I and II. Former studies have confirmed that the bladder is also considered to be one of the immune attacked organs in acute graft-versus-host disease (aGVHD). The classic treatments for HC include hydration, alkalization, and bladder irrigation, immunosuppressant reduction, and platelet transfusion. Patients with viral infection may be treated with antiviral agents, but their efficacy is limited. When the HC was considered to be associated with aGVHD, some immunosuppressive agents such as glucocorticoids will be added in. However, too intensive immunosuppressive measures leave the patients susceptible to infection and, in turn, increases the accidence of non-relapse mortality (NRM). The mechanism underlying the development of HC remains largely unidentified, and its optimal treatment has not yet been established. It is important to explore novel, less-toxic, higher effective, and cost-effective strategies to improve HC. The elevated levels of available oxygen and partial pressure of arterial oxygen provide the main benefits of Hyperbaric oxygen therapy (HBOT) in clinical practice that addresses these areas of inadequate or poor tissue healing. HBOT is utilized as primary or adjunctive therapy for many medical conditions in which tissue damage is triggered by hypoxic injury. The pharmacological and physiologic effects of HBOT have direct and indirect mechanisms and effects on reactive oxygen species (ROS) most beneficial to that of wound healing and antibacterial treatments. HBOT can stimulate fibroblast proliferation, angiogenesis, and wound healing. It has been shown effective in the treatment of radiation-induced HC by promoting fibroblast proliferation and capillary angiogenesis, decreasing edema, and facilitating damaged hypoxic urothelium. Based on the above clinical and pre-clinical practice, the investigators deduce that HBOT may benefit patients with HC after HSCT. In the investigators' limited early-onset investigation, the investigators found HBO was largely successful in 20 patients suffering HC post-allo-HSCT, showed a quick resolution or improvement of HC. The investigators also observed more rapid responses in patients who started HBOT earlier after the diagnosis of HC. The investigators confirmed that HBOT was effective and well-tolerated in the patients, regardless of the infective- or non-infective- caused HC. Therefore, the investigators design this prospective, randomized, and single-arm clinical trial to establish the definitive efficacy and safety of HBOT in patients with HC after allo-HSCT.

Conditions

Stem Cell Transplant Complications

Keywords

allogeneic stem cell transplantation; Hemorrhagic cystitis; Hyperbaric oxygen treatment

Outcome Measures

Primary Outcomes (2)

• Response rate of HBOT

  Response rate of HBOT was determined on the basis of HC symptom disppearance and the normal urine routine test result

  Six months post-allo-HSCT

• Incidence and severity of treatment-related adverse events

  Number of participants with treatment-related adverse events and the the severity of these events.

  3 years

Secondary Outcomes (1)

• Exploratory biomarker analysis

  3 years

Study Arms (1)

HBOT group

EXPERIMENTAL

Patients with hemorrhagic cystitis (HC) after allo-HSCT will receive hyperbaric oxygen therapy (HBOT) on the next day of the HC diagnosis was determined. Then HBOT will be scheduled every day until symptoms of HC vanished.

Procedure: Hyperbaric oxygen therapy

Interventions

Hyperbaric oxygen therapy PROCEDURE

Patients with hemorrhagic cystitis (HC) after allo-HSCT will receive hyperbaric oxygen therapy (HBOT) on the next day of the HC diagnosis was determined. Then HBOT will be scheduled every day until symptoms of HC vanished. Other classic measures to treatment HC such as hydration, alkalization, and bladder irrigation will also be carried out at the same time.

HBOT group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing allogeneic stem cell transplantation
• Patients develop late-onset hemorrhagic cystitis (HC)
• The count of neutrophilia cells over 0.5 \* 10\^9/L, hemoglobin over 60 g/L, platelet over 30 \*10\^9/L
• SGOT/SGPT no more than 2 times of UNL
• Serum creatinine no more than 1.5 times of UNL
• Signed informed consent

You may not qualify if:

• Early-onset HC post-allo-HSCT
• Unsuitable to the study due to severe complication such as uncontrolled severe infection
• Claustrophobia
• Ear diseases such as otitis media
• Eye diseases such as glaucoma
• Epilepsy history
• Important organ dysfunction
• Coagulopathy

Sponsors & Collaborators

• Shandong Provincial Hospital: lead

Study Sites (1)

Shandong Provincial Hospital

Jinan, Shandong, 250021, China

RECRUITING

Related Publications (1)

• Xue C, Chen H, Zhao Y, Yuan D, Fang X, Ding M, Qu H, Wang X, Ge X, Lu K, Jiang Y. Preventive hyperbaric oxygen therapy improves acute graft-versus-host disease by activating the Nrf2/HO-1 pathway. Front Immunol. 2025 Feb 27;16:1529176. doi: 10.3389/fimmu.2025.1529176. eCollection 2025.

  PMID: 40083556 DERIVED

MeSH Terms

Conditions

Cystitis, Hemorrhagic

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Cystitis; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Study Officials

• Xin Wang

  Shandong Provincial Hospital

  STUDY CHAIR

Central Study Contacts

Yujie M JIANG

CONTACT

8613370506886; yujiejiang05@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Hematology

Study Record Dates

• First Submitted: July 30, 2020
• First Posted: August 6, 2020
• Study Start: September 1, 2021
• Primary Completion: July 31, 2023
• Study Completion: December 31, 2024
• Last Updated: September 8, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)