Ignite Creation Date:
2026-03-26 @ 3:20 PM
Ignite Modification Date:
2026-03-31 @ 9:09 PM
Study NCT ID:
NCT07487220
Status:
COMPLETED
Last Update Posted:
2026-03-25
First Post:
2026-03-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Non-invasive Remote Ischemic PreConditioning (RIPC) in Free Flaps for Breast Reconstruction
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015427', 'term': 'Reperfusion Injury'}, {'id': 'D007511', 'term': 'Ischemia'}], 'ancestors': [{'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D011183', 'term': 'Postoperative Complications'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants undergoing free flap reconstruction will be randomly assigned to one of three parallel groups: (1) no remote ischemic conditioning (control), (2) remote ischemic conditioning 12-24 hours prior to surgery, or (3) remote ischemic conditioning immediately prior to surgery. Participants remain in their assigned study arm throughout the study period. In cases of postoperative flap perfusion compromise requiring revision surgery, participants will undergo a secondary randomization to receive either additional remote ischemic conditioning or no conditioning prior to revision.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 49}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-04-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-03', 'completionDateStruct': {'date': '2023-12-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2026-03-21', 'studyFirstSubmitDate': '2026-03-17', 'studyFirstSubmitQcDate': '2026-03-17', 'lastUpdatePostDateStruct': {'date': '2026-03-25', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-12-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Microcirculatory perfusion of free flap tissue measured by Laser-Doppler flowmetry and tissue spectrometry', 'timeFrame': 'From intraoperative revascularization until postoperative day 5', 'description': 'Continuous assessment of microcirculatory perfusion parameters of free flap tissue using combined Laser-Doppler flowmetry and tissue spectrometry (O2C system). Parameters include blood flow (BF), tissue oxygen saturation (StO₂), and relative hemoglobin concentration (rHb) measured in the transplanted tissue to evaluate the effect of remote ischemic conditioning on flap perfusion and ischemia-reperfusion injury.'}], 'secondaryOutcomes': [{'measure': 'Incidence of flap tissue necrosis following free flap reconstruction', 'timeFrame': 'Up to postoperative day 5', 'description': 'Occurrence and extent of partial or complete flap necrosis following free tissue transfer surgery, assessed clinically during the postoperative observation period.'}, {'measure': 'Histological markers of vascularization and ischemia-reperfusion injury in flap tissue', 'timeFrame': 'From intraoperative sampling after revascularization until postoperative day 5-7', 'description': 'Histological and immunohistochemical analysis of tissue biopsies obtained from the transplanted flap to assess vascularization, cellular damage, inflammatory response, and expression of ischemia-reperfusion related proteins (e.g., HIF1α, VEGF, TNFα, IL-1β). Analyses are performed on intraoperative and postoperative tissue samples to evaluate the biological effects of remote ischemic conditioning.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['ischemia', 'reperfusion', 'free flap', 'Wound Healing'], 'conditions': ['Ischemia-Reperfusion Injury', 'Free Flap', 'Conditioning Therapy']}, 'referencesModule': {'references': [{'pmid': '41381697', 'type': 'RESULT', 'citation': 'Drysch M, Fiedler A, Schmidt SV, Reinkemeier F, Puscz F, Kurbacher T, Frey UH, Ochsenfarth C, Lehnhardt M, Wallner C, Sogorski A. Systemic downregulation of EV-associated MiRNAs following remote ischemic preconditioning. Sci Rep. 2025 Dec 11;15(1):43657. doi: 10.1038/s41598-025-31356-9.'}, {'pmid': '40771071', 'type': 'RESULT', 'citation': 'Drysch M, Fiedler A, Kurbacher T, Schmidt SV, Reinkemeier F, Puscz F, Becerikli M, Fueth M, Weskamp P, Lehnhardt M, Wallner C, Sogorski A. Ischemia-Reperfusion Injury in Free Flaps: Molecular Mechanisms and Protective Effects of Remote Ischemic Preconditioning. J Cell Mol Med. 2025 Aug;29(15):e70739. doi: 10.1111/jcmm.70739.'}]}, 'descriptionModule': {'briefSummary': 'This prospective randomized clinical study investigates the effects of Remote Ischemic Conditioning (RIC) on tissue perfusion and ischemia-reperfusion injury in patients undergoing free flap reconstruction in reconstructive microsurgery. RIC is a non-invasive conditioning technique using cyclic ischemia and reperfusion applied to an extremity, which may enhance microcirculation and induce tissue protection.\n\nThe study aims to evaluate whether preoperative RIC improves postoperative flap perfusion, reduces ischemia-reperfusion- related tissue damage, and enhances clinical outcomes such as flap survival, wound healing, and need for revision surgery. Patients undergoing free flap procedures will be randomized to receive either preoperative RIC (immediate or delayed) or no conditioning.\n\nAdditional analyses include continuous postoperative monitoring of microcirculation, histological and molecular assessment of tissue samples, and evaluation of circulating biomarkers associated with tissue protection.', 'detailedDescription': 'Background Free flap reconstruction represents the gold standard for complex soft tissue defects arising from tumor resection, trauma, or chronic wounds. Despite refinements in microsurgical technique and perioperative management, flap-related complications, including partial necrosis, wound healing disorders, and total flap loss, continue to occur at clinically meaningful rates. The underlying pathophysiology involves obligatory ischemia during flap harvest and transfer, followed by reperfusion upon anastomosis completion. This ischemia-reperfusion (I/R) sequence triggers a cascade of oxidative stress, endothelial dysfunction, inflammatory activation, and microcirculatory failure that can ultimately compromise tissue viability.\n\nCurrent intraoperative strategies to mitigate I/R injury remain limited, and no pharmacological or mechanical intervention has been established as standard of care in this context.\n\nScientific Rationale for Remote Ischemic Conditioning Remote Ischemic Conditioning (RIC) exploits the endogenous capacity of biological tissue to develop tolerance to ischemic stress when exposed to brief, non-lethal cycles of ischemia and reperfusion at a site distant from the target organ. Originally described in cardiac surgery, RIC has since been investigated across a range of ischemia-sensitive tissues and clinical scenarios. Proposed mechanisms include neuronal and humoral signaling pathways that activate cytoprotective programs, such as upregulation of heat shock proteins, modulation of the RISK (Reperfusion Injury Salvage Kinase) pathway, suppression of mitochondrial permeability transition pore opening, and attenuation of neutrophil-mediated endothelial injury.\n\nPreclinical models of pedicled and free flaps have demonstrated improved perfusion, reduced apoptosis, and enhanced flap survival following RIC. However, these findings have not yet been translated into a prospective randomized clinical trial in reconstructive microsurgery.\n\nTiming of Conditioning: Study Design Rationale A key unresolved question concerns the optimal timing of RIC relative to surgery. Two biologically distinct windows of protection have been described: an immediate window (within approximately 1-2 hours of the conditioning stimulus, mediated largely by post-translational protein modifications) and a delayed window (emerging 12\\*24 hours later, dependent on de novo protein synthesis and gene expression changes). To address this, the trial incorporates three parallel arms: a non-conditioned control group, an immediately preconditioned group (approximately 1 hour before surgery), and a delayed preconditioned group (12-24 hours preoperatively). This design enables direct comparison of both conditioning windows against each other and against standard care.\n\nIn cases where intraoperative findings necessitate unplanned revision surgery, a secondary randomization procedure is pre-specified to evaluate the potential benefit of RIC in the setting of threatened flap perfusion.\n\nIntervention Protocol RIC is applied non-invasively to the upper arm using a standard pneumatic tourniquet. Each conditioning session consists of three alternating cycles of 10-minute ischemia (cuff inflated to approximately 250 mmHg, sufficient to occlude arterial inflow) and 10-minute reperfusion (cuff deflated), for a total session duration of 60 minutes. This protocol is consistent with those used in cardiovascular RIC trials and has a well-characterized safety profile.\n\nMicrocirculatory Monitoring Postoperative flap perfusion will be continuously assessed using a multimodal approach combining laser Doppler flowmetry and tissue spectrometry (O2C device or equivalent). These complementary techniques enable real-time, non-invasive quantification of microvascular flow, tissue oxygen saturation, and relative hemoglobin concentration. Measurements will be obtained at standardized time points throughout the first five postoperative days, allowing construction of perfusion trajectories and identification of early signs of compromised microcirculation.\n\nTissue and Biomarker Analyses Standardized biopsies will be obtained from clinically non-essential portions of the flap at defined intraoperative and early postoperative time points. Samples will undergo histological and immunohistochemical evaluation for markers of ischemic injury, cellular stress responses, inflammatory infiltration, and apoptosis. Parallel molecular analyses will characterize expression of proteins and signaling mediators implicated in I/R injury and cytoprotection.\n\nSerial blood samples will be collected perioperatively to quantify circulating biomarkers, including but not limited to markers of oxidative damage, endothelial activation, and systemic inflammatory response. These analyses serve both to detect systemic correlates of local tissue protection and to identify candidate biomarkers for future use in monitoring RIC efficacy.\n\nClinical Outcome Assessment In addition to mechanistic endpoints, the trial will capture a comprehensive set of clinical outcomes through postoperative day 5 and beyond, including flap survival rate, incidence and severity of wound healing disorders, requirement for revision surgery or re-anastomosis, and total length of inpatient stay. Adverse events and protocol deviations will be systematically recorded.\n\nStatistical Considerations Sample size estimation is based on the primary perfusion endpoint. Randomization will be performed centrally with stratification for relevant clinical variables. All primary analyses will follow the intention-to-treat principle; per-protocol analyses will be conducted as sensitivity analyses.\n\nSignificance If RIC is demonstrated to improve perfusion and reduce I/R injury in this setting, it would offer a compelling adjunct to reconstructive microsurgery: it is non-invasive, requires no specialized pharmacology, adds minimal procedural complexity, and is associated with a favorable safety profile in other surgical disciplines. The results of this trial are expected to inform evidence-based guidelines for perioperative conditioning in free flap surgery and to lay the groundwork for larger multicenter investigations.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 18 years\n* Patients undergoing free flap reconstruction surgery for reconstruction of body surface defects\n* Treatment at the Department of Plastic Surgery, BG Universitätsklinikum Bergmannsheil Bochum\n* Ability to understand the study procedures\n* Written informed consent to participate in the study\n\nExclusion Criteria:\n\n* Refusal or inability to provide informed consent\n* Contraindications to regional nerve block or perioperative procedures required for the study\n* Any condition that prevents participation according to investigator judgment'}, 'identificationModule': {'nctId': 'NCT07487220', 'acronym': 'RIPC', 'briefTitle': 'Non-invasive Remote Ischemic PreConditioning (RIPC) in Free Flaps for Breast Reconstruction', 'organization': {'class': 'OTHER', 'fullName': 'Ruhr University of Bochum'}, 'officialTitle': 'Non-invasive Remote Ischemic PreConditioning in Free Flaps for Breast Reconstruction', 'orgStudyIdInfo': {'id': '19-6752'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'NO_INTERVENTION', 'label': 'No RIPC', 'description': 'No Remote Ischemic Conditioning (RIC) is administered. Participants receive standard perioperative care and undergo free flap reconstruction according to institutional protocols without any preconditioning intervention.'}, {'type': 'EXPERIMENTAL', 'label': 'Early RIPC', 'description': 'Remote Ischemic Conditioning (RIC) is performed 12-24 hours prior to surgery. The intervention consists of three cycles of ischemia and reperfusion applied to the upper arm using a pneumatic tourniquet. Each cycle includes 10 minutes of ischemia (inflation to approximately 250 mmHg) followed by 10 minutes of reperfusion (deflation). The total duration of the conditioning procedure is 60 minutes. Participants subsequently undergo free flap reconstruction according to standard institutional protocols.', 'interventionNames': ['Device: Remote ischemic preconditiong']}, {'type': 'EXPERIMENTAL', 'label': 'Late RIPC', 'description': 'Remote Ischemic Conditioning (RIC) is performed one hour prior to surgery. The intervention consists of three cycles of ischemia and reperfusion applied to the upper arm using a pneumatic tourniquet. Each cycle includes 10 minutes of ischemia (inflation to approximately 250 mmHg) followed by 10 minutes of reperfusion (deflation). The total duration of the conditioning procedure is 60 minutes. Participants subsequently undergo free flap reconstruction according to standard institutional protocols.', 'interventionNames': ['Device: Remote ischemic preconditiong']}], 'interventions': [{'name': 'Remote ischemic preconditiong', 'type': 'DEVICE', 'description': 'The intervention consists of three cycles of ischemia and reperfusion applied to the upper arm using a pneumatic tourniquet. Each cycle includes 10 minutes of ischemia (inflation to approximately 250 mmHg) followed by 10 minutes of reperfusion (deflation). The total duration of the conditioning procedure is 60 minutes. Participants subsequently undergo free flap reconstruction according to standard institutional protocols.', 'armGroupLabels': ['Early RIPC', 'Late RIPC']}]}, 'contactsLocationsModule': {'locations': [{'zip': '44789', 'city': 'Bochum', 'state': 'North Rhine-Westphalia', 'country': 'Germany', 'facility': 'BG University Clinic Bergmannsheil', 'geoPoint': {'lat': 51.48165, 'lon': 7.21648}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Individual participant data collected in this study will not be made publicly available. All study data will be pseudonymized and stored on secure institutional servers with access restricted to authorized study personnel. Data are collected as part of a single-center clinical study and contain potentially identifiable clinical information. Aggregated results may be published in scientific journals, but individual-level data will not be shared outside the study team in order to protect participant confidentiality.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Ruhr University of Bochum', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Resident Physician, Department of Plastic, Reconstructive and Burn Surgery', 'investigatorFullName': 'ALEXANDER FIEDLER', 'investigatorAffiliation': 'Ruhr University of Bochum'}}}}