Amputation; Postoperative, Sequelae
Conditions
Brief summary
This study is being conducted to assess the utility of hyperbaric oxygen as an adjunctive treatment to reduce postoperative complications. It is hypothesized that HBO2 given in the immediate postoperative period will reduce postoperative complications in patients undergoing below-the-knee amputations. The objective of this study will be to compare treatment and standard care groups, randomly created of eligible patients, to compare their postoperative complications and to assess their postoperative hospital length of stay, 90-day mortality, failure to heal at 4 and 8 week follow-up visits and ability to ambulate with a prosthesis at 6 months post amputation.
Detailed description
This is a clinical study to test the hypothesis that Hyperbaric Oxygen (HBO2) given in the immediate postoperative period for a total of 10 treatments after Below-the-Knee Amputation (BKA) for vascular disease will reduce postoperative complications. Patients scheduled for BKA at Duke University Medical Center will be reviewed for contraindications to HBO2. Patients for whom HBO2 is not contraindicated may choose to be enrolled in the study. Patients enrolled will be randomly assigned to receive treatment or standard postoperative care. Each patient receiving treatment will receive twice daily HBO2 for 2 hours at breathing 100% oxygen at 2 atmospheres absolute (ATA). Patients receiving HBO2 will breathe 100% oxygen via head tent while inside a hyperbaric chamber at Duke University Hospital. The statistical plan for this study will test non-directional hypotheses (two-sided tests). Bonferroni correction will be used to adjust for multiple tests. The main analysis of the primary efficacy hypotheses will include data from all randomized patients in the group to which random assignment is made. Hence, the analysis will be intention to treat. This study will primarily aim to assess whether patients receiving treatment suffer fewer complications, as defined by the Vascular Quality Initiative, vs. patients who receive standard care. The Vascular Quality Initiative (VQI) is a multicenter voluntary reporting system for outcomes related to vascular surgery. The primary outcome of this study, postoperative complications, will be those outcomes meeting the definition set out in the VQI data dictionary, the set of definitions for inclusion in the VQI database. This allows for a standard definition of complications recognized by a majority of US academic medical centers. Secondary outcomes include hospital length of stay, 90-day mortality, failure to heal at 4 and 8 week follow-up visits and ability to ambulate with a prosthesis at 6 months post amputation.
Interventions
DRUGHyperbaric Oxygen
Hyperbaric oxygen (HBO2) 1-2 times daily for up to 10 times after amputation
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Permuted block
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to consent * Non-traumatic indication for lower limb amputation * Able to receive hyperbaric oxygen therapy
Exclusion criteria
* Unable to consent * Contraindication to hyperbaric oxygen * End stage renal disease on dialysis * Current renal failure as measured by creatinine levels vs baseline change of more than 1 mg/dL and for whom dialysis is expected to be required with the next month * Calciphylaxis * Traumatic injuries that are the cause of the amputation * Cancer being treated by chemotherapy, scheduled to be treated, or being treated or scheduled to be treated by radiation. * Limb amputation secondary to ischemic complications from other operations * Second amputation or reoperation on prior amputation * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Wound Infection | Up to 90 days after amputation | Any wound site infection that was culture positive or required antibiotic treatment |
| Number of Participants With Mortality During the Inpatient Period | During inpatient stay immediately after amputation, up to 13 days | — |
| Number of Participants With Re-operation | Up to 90 days after amputation | Unplanned return to the OR (operating room) for a surgical procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Healing of Amputation Wound Healing at 4 Weeks Following Surgery | 4 weeks after amputation | Complete wound healing at 4 weeks after amputation |
| Number of Participants Able to Ambulate With Prosthesis | 6 months after amputation | Ability to ambulate with a prosthesis at 6 months post amputation |
| Number of Participants With Complete Healing of Amputation Wound Healing at 8 Weeks Following Surgery | 8 weeks after amputation | Complete wound healing at 8 weeks after amputation |
| Hospital Length of Stay | up to approximately 30 days | Hospital length of stay immediately after amputation |
| Number of Participants With 90-day Mortality | Up to 90 days after amputation | Death within 90 days after amputation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hospital Readmission | Up to 90 days after amputation | Any readmission to hospital after initial discharge |
Countries
United States
Participant flow
Recruitment details
Recruitment was in hospital.
Participants by arm
| Arm | Count |
|---|---|
| Hyperbaric Oxygen Plus Regular Care Hyperbaric oxygen (2 hours at 2 atmospheres absolute) to be administered 1-2 times daily for up to 10 treatments after amputation. Usual care for patients with amputation will be administered in parallel.
Hyperbaric Oxygen: Hyperbaric oxygen (HBO2) 1-2 times daily for up to 10 times after amputation | 3 |
| Regular Care Usual care for patients with amputation. | 1 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Hyperbaric Oxygen Plus Regular Care | Regular Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Continuous | 52 years | 74 years | 57.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 3 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 0 / 1 |
| other Total, other adverse events | 0 / 3 | 0 / 1 |
| serious Total, serious adverse events | 0 / 3 | 0 / 1 |
Outcome results
Primary
Number of Participants With Mortality During the Inpatient Period
Time frame: During inpatient stay immediately after amputation, up to 13 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperbaric Oxygen Plus Regular Care | Number of Participants With Mortality During the Inpatient Period | 1 Participants |
| Regular Care | Number of Participants With Mortality During the Inpatient Period | 0 Participants |
p-value: 1Chi-squared
p-value: >0.5Chi-squared, Corrected
Primary
Number of Participants With Re-operation
Unplanned return to the OR (operating room) for a surgical procedure
Time frame: Up to 90 days after amputation
Population: One participant in the Hyperbaric Oxygen Plus Regular Care arm died following amputation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperbaric Oxygen Plus Regular Care | Number of Participants With Re-operation | 0 Participants |
| Regular Care | Number of Participants With Re-operation | 0 Participants |
p-value: >0.5Chi-squared, Corrected
Primary
Number of Participants With Wound Infection
Any wound site infection that was culture positive or required antibiotic treatment
Time frame: Up to 90 days after amputation
Population: One participant in the Hyperbaric Oxygen Plus Regular Care arm died following amputation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperbaric Oxygen Plus Regular Care | Number of Participants With Wound Infection | 0 Participants |
| Regular Care | Number of Participants With Wound Infection | 0 Participants |
p-value: >0.5Chi-squared, Corrected
Secondary
Hospital Length of Stay
Hospital length of stay immediately after amputation
Time frame: up to approximately 30 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hyperbaric Oxygen Plus Regular Care | Hospital Length of Stay | 5.3 days |
| Regular Care | Hospital Length of Stay | 13 days |
p-value: >0.5t-test, 2 sided
Secondary
Number of Participants Able to Ambulate With Prosthesis
Ability to ambulate with a prosthesis at 6 months post amputation
Time frame: 6 months after amputation
Population: One participant in the Hyperbaric Oxygen Plus Regular Care arm died following amputation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperbaric Oxygen Plus Regular Care | Number of Participants Able to Ambulate With Prosthesis | 2 Participants |
| Regular Care | Number of Participants Able to Ambulate With Prosthesis | 0 Participants |
p-value: >0.5Chi-squared, Corrected
Secondary
Number of Participants With 90-day Mortality
Death within 90 days after amputation
Time frame: Up to 90 days after amputation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperbaric Oxygen Plus Regular Care | Number of Participants With 90-day Mortality | 1 Participants |
| Regular Care | Number of Participants With 90-day Mortality | 0 Participants |
Comparison: Underpowered - no statistically significant difference.p-value: >0.5Cochran-Mantel-Haenszel
Secondary
Number of Participants With Complete Healing of Amputation Wound Healing at 4 Weeks Following Surgery
Complete wound healing at 4 weeks after amputation
Time frame: 4 weeks after amputation
Population: One participant in the Hyperbaric Oxygen Plus Regular Care arm died following amputation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperbaric Oxygen Plus Regular Care | Number of Participants With Complete Healing of Amputation Wound Healing at 4 Weeks Following Surgery | 0 Participants |
| Regular Care | Number of Participants With Complete Healing of Amputation Wound Healing at 4 Weeks Following Surgery | 0 Participants |
p-value: >0.5Chi-squared, Corrected
Secondary
Number of Participants With Complete Healing of Amputation Wound Healing at 8 Weeks Following Surgery
Complete wound healing at 8 weeks after amputation
Time frame: 8 weeks after amputation
Population: One participant in the Hyperbaric Oxygen Plus Regular Care arm died following amputation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperbaric Oxygen Plus Regular Care | Number of Participants With Complete Healing of Amputation Wound Healing at 8 Weeks Following Surgery | 1 Participants |
| Regular Care | Number of Participants With Complete Healing of Amputation Wound Healing at 8 Weeks Following Surgery | 0 Participants |
p-value: >0.5Chi-squared, Corrected
Other Pre-specified
Number of Participants With Hospital Readmission
Any readmission to hospital after initial discharge
Time frame: Up to 90 days after amputation
Population: One participant in the Hyperbaric Oxygen Plus Regular Care arm died following amputation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hyperbaric Oxygen Plus Regular Care | Number of Participants With Hospital Readmission | 0 Participants |
| Regular Care | Number of Participants With Hospital Readmission | 1 Participants |
p-value: >0.5Chi-squared, Corrected