Hyperbaric Oxygen Therapy for Hemorrhagic Cystitis Post HSCT

Hyperbaric Oxygen Therapy for the Treatment of Hemorrhagic Cystitis Post Allogeneic Hematopoietic Stem Cell Transplantation

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.

Study Overview

• Status: Recruiting
• Conditions: Stem Cell Transplant Complications
• Intervention / Treatment: Procedure: Hyperbaric oxygen therapy

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yujie M JIANG; Phone Number: 8613370506886 8613370506886; Email: yujiejiang05@126.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250021
      • Recruiting
      • Shandong Provincial Hospital
      • Contact: Yujie JIANG; Phone Number: 8613370506886; Email: yujiejiang05@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HBOT group; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory biomarker analysis	Exploratory biomarker to predict treatment response	3 years

Collaborators and Investigators

• Sponsor: Shandong Provincial Hospital
• Investigators: Study Chair: Xin Wang, Shandong Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2021
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 6, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: allogeneic stem cell transplantation; Hemorrhagic cystitis; Hyperbaric oxygen treatment
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Cystitis
• Other Study ID Numbers: HBOT for HC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No