Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?

Phase 4

Active, not recruiting

• Conditions: Diabetic Foot Ulcer; Amputation; Peripheral Vascular Disease
• Interventions: Drug: Hyperbaric oxygen

• Registration Number: NCT05804097
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

The goal of this multicenter, multi-national, multi-arm, multi-stage, randomized controlled trial, is to determine the added benefit of hyperbaric oxygen treatment (HBOT) in patients with diabetic foot ulcers and peripheral vascular disease. The main question is:

- What is the difference is the major amputation rate between the study arms?

Participants will be randomized to 20, 30 or 40 sessions of HBOT or a control group.

Detailed Description

Objective: The primary objective is to assess the (cost-) effectiveness of HBOT in addition to standard wound care and vascular surgical treatment for patients with a DFU and leg ischaemia.

Study design: An international, multi-arm multi-stage (MAMS) design is chosen to conduct an efficient randomised clinical trial. At a planned interim analysis the best performing study arm(s) will be chosen to continue.

Study population: We need up to 544 patients with a Meggitt-Wagner stage 3 or 4 DFU and proven peripheral ischaemia.

Intervention: Patients will be randomised to receive standard care (wound treatment and surgical interventions following international guidelines) with either 0, 20, 30 or at least 40 sessions of HBOT. These sessions will compromise 90-120 minutes of HBOT at a pressure of 2.2-2.5 ATA according to international standards.

Main study parameters/endpoints: The primary endpoint is major amputation rate after 12 months. Secondary objectives are amputation-free survival, wound healing, health-related quality of life and cost-effectiveness of the interventions.

Study Timeline

• Study Start: 2021-10-08
• Study First Submitted: 2023-03-24
• Study First Submitted QC: 2023-04-05
• Study First Posted: 2023-04-07
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-08
• Primary Completion: 2025-05-01
• Study Completion: 2025-05-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Type I or II diabetes
2. One or more deep and clinically infected lower extremity ulcers, classified as Meggitt-Wagner class 3 or 4, Texas class 2C, 3C, 2D or 3D, or WIfI class W>1, I>1 and fI>0), present for at least 4 weeks or after a minor amputation because of a previously existing ischaemic DFU on a toe or forefoot. In case more than one ulcer is present, the largest will be observed as target ulcer
3. Leg ischaemia, characterized by a highest ankle systolic blood pressure < 70 mmHg, or a toe systolic pressure < 50 mmHg or a TcpO2 < 40 mmHg
4. Complete assessment of peripheral arterial lesions from the aorta to the pedal arteries with duplex ultrasonography, magnetic resonance angiography, computed tomography angiography and/or intraarterial digital subtraction angiography of the ipsilateral leg
5. Patients have to be discussed in, and included after a multidisciplinary consultation.
6. Adults
7. Written informed consent

Exclusion Criteria

1. Chronic Obstructive Pulmonary Disease (COPD) GOLD IV
2. Treatment with chemotherapy, immunosuppressive drugs or systemic corticosteroids within last 3 months, as this interferes with normal wound healing
3. End-stage renal disease requiring dialysis
4. Metastasized malignancy
5. Left ventricular failure with ejection fraction (EF) <20% or external pacemaker
6. Recent thoracic surgery or middle ear surgery
7. Severe epilepsy
8. Uncontrollable high fever
9. Pregnancy
10. Insufficient proficiency of local language/English, or inability to complete the questionnaires

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HBOT 20	Hyperbaric oxygen	Patients receiving 20 sessions of concurrent Hyperbaric oxygen treatment
HBOT 30	Hyperbaric oxygen	Patients receiving 30 sessions of concurrent Hyperbaric oxygen treatment
HBOT 40	Hyperbaric oxygen	Patients receiving at least 40 sessions of concurrent Hyperbaric oxygen treatment

Primary Outcome Measures

Name	Time	Method
Major Amputations	12 months after inclusion	Major amputations, defined as below the knee or above the knee amputations

Secondary Outcome Measures

Name	Time	Method
Health-related quality of life	Complete follow-up (up to 3 years)	Quality of life based on various questionnaires (objective)
Cost-effectiveness and budget impact	Complete follow-up (up to 3 years)	Costs of healthcare resources, including HBOT, related to the total number of eligible patients for HBOT per year.; QALYs, based on EQ-5D-5L
Patients perception of improvement	Complete follow-up (up to 3 years)	Quality of life based on various questionnaires (subjective)
Complete wound healing	12 months after inclusion	Complete wound healing
Pain scores	12 months after inclusion	Pain scores taken by VAS questionnaire
Need for additional (vascular) interventions	Complete follow-up (up to 3 years)	Vascular interventions performed during time of inclusion
Amputation-free survival	Complete follow-up (up to 3 years)	Time without amputation
Mortality	Complete follow-up (up to 3 years)	Mortality
TcpO2 before, during and after HBOT	During intervention period	Measurements of TcpO2 surrounding HBOT treatment

Trial Locations

Locations (1)

Amsterdam UMC; 🇳🇱 Amsterdam, Noord-Hollad, Netherlands