Ignite Creation Date:
2024-05-06 @ 3:31 PM
Last Modification Date:
2024-10-26 @ 1:51 PM
Study NCT ID:
NCT04665830
Status:
COMPLETED
Last Update Posted:
2020-12-14
First Post:
2020-12-07
Brief Title:
PCSK 9 Inhibition as Secondary Prevention in Renal Transplant Patients
Sponsor:
Hamid Al-Essa Organ Transplant Center
Organization:
Hamid Al-Essa Organ Transplant Center
Study Overview
Official Title:
PCSK 9 Inhibition as Secondary Prevention in Renal Transplant Patients With Cardiovascular Disease
Status:
COMPLETED
Status Verified Date:
2020-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
From this randomized controlled study we aim to
ADo do cardiovascular risk stratification of renal transplant recipients who are followed up in Hamed Al-Essa organ transplant center of Kuwait
B To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs maximum tolerated statin therapy alone in the reduction of major cardiovascular events among renal transplant recipients with cardiovascular disease
C To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs maximum tolerated statin therapy alone in terms of LDL-C-lowering muscle symptoms and quality of life
D To compare patient adherence to the different treatment protocols
ADo do cardiovascular risk stratification of renal transplant recipients who are followed up in Hamed Al-Essa organ transplant center of Kuwait
B To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs maximum tolerated statin therapy alone in the reduction of major cardiovascular events among renal transplant recipients with cardiovascular disease
C To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs maximum tolerated statin therapy alone in terms of LDL-C-lowering muscle symptoms and quality of life
D To compare patient adherence to the different treatment protocols
Detailed Description:
Background
Low-density lipoprotein LDL cholesterol is a well-established and modifiable risk factor for cardiovascular disease Monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 PCSK9 have emerged as a new class of drugs that effectively lower LDL cholesterol levels1 Approximately 735000 Americans have a myocardial infarction each year 2 and about 800000 have a stroke 3 Many patients remain at increased cardiovascular risk despite maximum tolerated statin therapy and could benefit from further LDL-C reduction Most patients are treated with HMG-CoA reductase inhibitors commonly known as statins Millions of patients are eligible for cholesterol-lowering medication according to current guidelines4 High-intensity statin therapy reduces LDL-C and cardiovascular events more than moderate intensity statin therapy 5 However the response to statins is variable and in some patients it is not tolerable between 7 percent and 29 percent of patients taking statins report having muscle symptoms 6 which represent a principal reason for nonadherence Moreover high-intensity statin therapy may have less benefit in low-risk primary prevention patients with a modest increase in the incidence of diabetes in such cases 5 7 Proprotein convertase subtilisinkexin type 9 PCSK9 inhibitors are currently indicated for some patients at high risk including those with familial hypercholesterolemia or pre-existing cardiovascular disease PCSK9 inhibitors are a new class of medications that have been found to be very effective in reducing LDL-C either as monotherapy or when added to background statin therapy Normally PCSK9 binds to low-density lipoprotein cholesterol LDL-C receptors reducing the activity of the LDL-C receptors PCSK9 inhibitors prevent PCSK9 from binding to the LDL receptor thereby increasing the activity of the receptors and enhancing removal of LDL-C from circulation 8 Current guidelines recommend that patients whose 10-year risk of major cardiovascular events is 10 percent or greater take statins 9 Two PCSK9 inhibitors are currently available and approved by FDA for use in the United States evolocumab and alirocumab These drugs are monoclonal antibodies mAbs administered by Proposed Clinical Trial Protocol on Use of PCSK9 Inhibitors for Primary Prevention of Cardiovascular Disease 3 subcutaneous injection bi-weekly or monthly and are currently approved for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C Two recent reports on the effects of evolocumab and alirocumab have raised expectations that these drugs will dramatically reduce cardiovascular events1011 the rate of major cardiovascular events was lower with alirocumab than with placebo 17 percent versus 33 percent hazard ratio 052 95 percent confidence interval 031 to 090 P002 11 Notably the annual cost for a single patient in the United States for PCSK9 inhibitors is approximately 140009 The prevalence of cardiovascular diseases CVD has increased in kidney transplant recipients CVD remains a leading cause of mortality among recipients with functioning grafts The pathophysiology of CVD recipients is a complex interplay between preexisting risk factors metabolic sequelae of immunosuppressive agents infection and rejection17
Aim of the study
A Cardiovascular risk stratification of renal transplant recipients who are followed up in Hamed Al-Essa organ transplant center of Kuwait
B To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs maximum tolerated statin therapy alone in the reduction of major cardiovascular events among renal transplant recipients with cardiovascular disease
C To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs maximum tolerated statin therapy alone in terms of LDL-C-lowering muscle symptoms and quality of life
D To compare patient adherence to the different treatments protocols
Patient and methods
Patients eligible for participation in this study are renal transplant recipients aged between 30 and 80 years and have clinically evident atherosclerotic cardiovascular disease defined as a history of myocardial infarction non-hemorrhagic stroke or symptomatic peripheral artery disease as well as additional characteristics that placed them at higher cardiovascular risk
This group of patients will be selected after screening of all renal transplant recipients who are followed up in Hamed Al-Essa organ transplant center of Kuwait along 6 months duration Cardio-vascular risk score will be estimated using Framingham score Patients with score higher than 20 will be randomized in this prospective controlled study to receive either the evolocumab group 1 n100 patients or the conventional group group 2 n100 patients
The selection criteria
1 Signed informed consent 2 Male or female Kuwaiti older than 30 and younger than 80 years of age at signing of informed consent 3 History of clinically evident cardiovascular diseasediagnosis of myocardial infarction non-hemorrhagic stroke or symptomatic peripheral arterial disease PAD as evidenced by intermittent claudication with ankle-brachial index ABI 085 or peripheral arterial revascularization procedure or amputation due to atherosclerotic disease 4 At least 1 major risk factor or at least 2 minor risk factors below Major Risk Factors 1 Required o diabetes type 1 or type 2 o age 65 years at randomization and 85 years at time of informed consent o MI or non-hemorrhagic stroke within 6 months of screening o additional diagnosis of myocardial infarction or non-hemorrhagic stroke excluding qualifying MI or non-hemorrhagic stroke o current daily cigarette smoking o history of symptomatic PAD as mentioned before if eligible by MI or stroke history Minor Risk Factors 2 Required o history of non-MI related coronary revascularization o residual coronary artery disease with 40 stenosis in 2 large vessels o Most recent HDL-C 10 mmolL for men and 13 mmolL for women by central laboratory before randomization o Most recent CRP 20 mgL by central laboratory before randomization o Most recent LDL-C 34 mmolL or non-HDL-C 41 mmolL by central laboratory before randomization o metabolic syndrome
Exclusion Criteria
1 Recent MI or stroke 2 NYHA class III or IV or last known left ventricular ejection fraction 30 3 Known hemorrhagic stroke at any time 4 Uncontrolled or recurrent ventricular tachycardia 5 Planned or expected cardiac surgery or revascularization within 3 months after randomization 6 Uncontrolled hypertension sitting systolic blood pressure SBP 180 mmHg or diastolic BP DBP 110 mmHg 7 Prior use of PCSK9 inhibition treatment other than evolocumab or use of evolocumab 12 weeks prior to final lipid screening 8 Untreated or inadequately treated hyperthyroidism or hypothyroidism thyroid stimulating hormone TSH lower limit of normal or 15 times the upper limit of normal and free thyroxine T4 levels that are outside normal range at final screening 9 Severe renal graft dysfunctionestimated glomerular filtration rate eGFR 20 mLmin173m2 at final screening 10 Active liver disease or hepatic dysfunction defined as aspartate aminotransferase AST or alanine aminotransferase ALT 3 times the ULN as determined by central laboratory analysis at final screening 11 Personal or family history of hereditary muscular disorders 12 Malignancy or HIV patients 13 Known major active infection or major hematologic metabolic gastrointestinal or endocrine dysfunction in the judgment of the investigator 13 Female subject who has either 1 not used acceptable methods of birth control for at least 1 month prior to screening or 2 is not willing to use such a method during treatment with IP and for an additional 15 weeks after the end of treatment with IP unless the subject is sterilized or postmenopausal 23 Known sensitivity to any of the active substances or their excipients to be administered during dosing
Methods
The baseline characteristics of the patients in the two groups will be collected with special stress on demographic data history of myocardial infarction history of previous non-hemorrhagic stroke and symptomatic peripheral artery disease At baseline all patients will be on statin therapy defined in accordance with American College of Cardiology and American Heart Association joint guidelines12 and or ezetimibe All antihypertensive medications antiplatelet and diuretic therapy will be recorded The duration of follow-up will be 12 months
Randomization
Eligible patients will be randomly assigned in a 11 ratio to receive subcutaneous injections of evolocumab either 140 mg every 2 weeks or matching placebo Randomization will be performed in a double-blinded manner with the use of a central computerized system with stratification according to the final screening LDL cholesterol level 22 or 22 mmol per liter and region
Follow up
All patients will be followed up in Hamed Al-Essa organ transplant center clinics at least every 2 months or according the local follow up protocol Patients who have a fasting LDL cholesterol level of 18 mmol per liter or higher or a non-high-density lipoprotein HDL cholesterol level of 26 mmol per liter or higher while they were taking an optimized regimen of lipid-lowering therapy which was defined as preferably a high intensity statin but must have been at least atorvastatin at a dose of 20 mg daily with or without ezetimibe
Our immunosuppression protocol consists of 5 doses of antithymocyte globulin Sanofi US Bridgewater NJ USA for high risk patients as re-transplants prior pregnancy blood transfusion HLA-antibody positive and or more than 4 HLA mismatchesor 2 doses of IL-2 receptor blocker basiliximab Novartis Inc Switzerland for low risk patients Maintenance therapy consists of prednisolone MMF and a calcineurin inhibitor CNI The dose of CNI will be gradually decreasing till the lowest dose by the end of the 1st year guided by 12-hour trough level We keep the cyclosporine A level between 200 to 250 ngml during 1st month then between 150-200 ngml for a couple of months then between 125-150 ngml for 2 months and from 75-125 ngml till the end of the 1st year Similarly we keep tacrolimus trough levels between 8 to 10 ngml during 1st 3 months then from 5-8 ngml thereafter Maintenance immunosuppression with sirolimus based regimen will be used to rejection free patients with low immunological risk after 3 months of transplantation
Acute cellular rejection ACR will be treated with intravenous methylprednisolone sodium succinate solumedrol 1 gram daily for 3 days and or thymoglobulin 1 mg kg for 7 -10 days for steroid resistant rejection Antibody mediated rejection AAMR will be treated with plasma exchange IVIG 2gmkg and rituximab Patients who will receive thymoglobulin as antirejection will be managed by secondary prophylaxis for 1 month Patients will be monitored daily during hospital stay then at each outpatient visit with complete blood picture serum creatinine creatinine clearance liver function tests bilirubin liver enzymes and albumin and drug levels
Lipid Data
The LDL cholesterol level will be checked in the central laboratory for all patients in both groups at baseline according to routine laboratory analysis and every third month using desktop Mission CE0123 cholesterol monitoring machine till the end of the study
End Points
The primary efficacy end point will be any major cardiovascular events defined as the cardiovascular death myocardial infarction stroke hospitalization for unstable angina or coronary revascularization The key secondary efficacy end point will be cardiovascular death myocardial infarction or stroke Safety was assessed through collection of data on adverse events and central laboratory testing in Ibn Sina laboratory Sabah area of Kuwait
Statistics and sample size calculation
Statistical analysis of data will be evaluated on computer using SPSS Statistical Package for Social Science for Windows 110 package software SPSS Inc Chicago IL USA In order to analyze the identifying and disease related characteristics of patients matched t-test will be used to compare means and standard deviations of numerical variables of the two groups and to test whether there will be a difference between pre-education and post-education score averages Categorical data will be compared using the chi square test Values for P less than 05 were considered significant
Confidentiality and consent
To maintain confidentiality all research data blood andurine specimens Consent Forms Data Collection Forms reports and other records that leave the site will be identified only by a Code Number-participant identification number Participant ID All records will be kept in a locked file cabinet All computer entry and networking programs will be done using PIDs only Participants identifiable private information will not be released to a third party without written permission of the participants
Detailed information will be delivered to each patient about the study including the aim and benefits Before starting the enrolment of each patient the investigator will get signed informed consent which will be kept in patient file Moreover a copy of this consent will be given to the patient
We will exclude participants with diminished capacity such as minors and mentally retarded who cannot consent for themselves from this study
The original copy of the consent will be kept in the investigators records a copy will be given to each participant and this will be documented in the participants record
The primary investigator and co-primary investigators will be responsible for implementing the consenting process and obtaining the Informed Consent of Participants
Low-density lipoprotein LDL cholesterol is a well-established and modifiable risk factor for cardiovascular disease Monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 PCSK9 have emerged as a new class of drugs that effectively lower LDL cholesterol levels1 Approximately 735000 Americans have a myocardial infarction each year 2 and about 800000 have a stroke 3 Many patients remain at increased cardiovascular risk despite maximum tolerated statin therapy and could benefit from further LDL-C reduction Most patients are treated with HMG-CoA reductase inhibitors commonly known as statins Millions of patients are eligible for cholesterol-lowering medication according to current guidelines4 High-intensity statin therapy reduces LDL-C and cardiovascular events more than moderate intensity statin therapy 5 However the response to statins is variable and in some patients it is not tolerable between 7 percent and 29 percent of patients taking statins report having muscle symptoms 6 which represent a principal reason for nonadherence Moreover high-intensity statin therapy may have less benefit in low-risk primary prevention patients with a modest increase in the incidence of diabetes in such cases 5 7 Proprotein convertase subtilisinkexin type 9 PCSK9 inhibitors are currently indicated for some patients at high risk including those with familial hypercholesterolemia or pre-existing cardiovascular disease PCSK9 inhibitors are a new class of medications that have been found to be very effective in reducing LDL-C either as monotherapy or when added to background statin therapy Normally PCSK9 binds to low-density lipoprotein cholesterol LDL-C receptors reducing the activity of the LDL-C receptors PCSK9 inhibitors prevent PCSK9 from binding to the LDL receptor thereby increasing the activity of the receptors and enhancing removal of LDL-C from circulation 8 Current guidelines recommend that patients whose 10-year risk of major cardiovascular events is 10 percent or greater take statins 9 Two PCSK9 inhibitors are currently available and approved by FDA for use in the United States evolocumab and alirocumab These drugs are monoclonal antibodies mAbs administered by Proposed Clinical Trial Protocol on Use of PCSK9 Inhibitors for Primary Prevention of Cardiovascular Disease 3 subcutaneous injection bi-weekly or monthly and are currently approved for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C Two recent reports on the effects of evolocumab and alirocumab have raised expectations that these drugs will dramatically reduce cardiovascular events1011 the rate of major cardiovascular events was lower with alirocumab than with placebo 17 percent versus 33 percent hazard ratio 052 95 percent confidence interval 031 to 090 P002 11 Notably the annual cost for a single patient in the United States for PCSK9 inhibitors is approximately 140009 The prevalence of cardiovascular diseases CVD has increased in kidney transplant recipients CVD remains a leading cause of mortality among recipients with functioning grafts The pathophysiology of CVD recipients is a complex interplay between preexisting risk factors metabolic sequelae of immunosuppressive agents infection and rejection17
Aim of the study
A Cardiovascular risk stratification of renal transplant recipients who are followed up in Hamed Al-Essa organ transplant center of Kuwait
B To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs maximum tolerated statin therapy alone in the reduction of major cardiovascular events among renal transplant recipients with cardiovascular disease
C To compare the effectiveness of a PCSK9 inhibitor plus maximum tolerated statin therapy vs maximum tolerated statin therapy alone in terms of LDL-C-lowering muscle symptoms and quality of life
D To compare patient adherence to the different treatments protocols
Patient and methods
Patients eligible for participation in this study are renal transplant recipients aged between 30 and 80 years and have clinically evident atherosclerotic cardiovascular disease defined as a history of myocardial infarction non-hemorrhagic stroke or symptomatic peripheral artery disease as well as additional characteristics that placed them at higher cardiovascular risk
This group of patients will be selected after screening of all renal transplant recipients who are followed up in Hamed Al-Essa organ transplant center of Kuwait along 6 months duration Cardio-vascular risk score will be estimated using Framingham score Patients with score higher than 20 will be randomized in this prospective controlled study to receive either the evolocumab group 1 n100 patients or the conventional group group 2 n100 patients
The selection criteria
1 Signed informed consent 2 Male or female Kuwaiti older than 30 and younger than 80 years of age at signing of informed consent 3 History of clinically evident cardiovascular diseasediagnosis of myocardial infarction non-hemorrhagic stroke or symptomatic peripheral arterial disease PAD as evidenced by intermittent claudication with ankle-brachial index ABI 085 or peripheral arterial revascularization procedure or amputation due to atherosclerotic disease 4 At least 1 major risk factor or at least 2 minor risk factors below Major Risk Factors 1 Required o diabetes type 1 or type 2 o age 65 years at randomization and 85 years at time of informed consent o MI or non-hemorrhagic stroke within 6 months of screening o additional diagnosis of myocardial infarction or non-hemorrhagic stroke excluding qualifying MI or non-hemorrhagic stroke o current daily cigarette smoking o history of symptomatic PAD as mentioned before if eligible by MI or stroke history Minor Risk Factors 2 Required o history of non-MI related coronary revascularization o residual coronary artery disease with 40 stenosis in 2 large vessels o Most recent HDL-C 10 mmolL for men and 13 mmolL for women by central laboratory before randomization o Most recent CRP 20 mgL by central laboratory before randomization o Most recent LDL-C 34 mmolL or non-HDL-C 41 mmolL by central laboratory before randomization o metabolic syndrome
Exclusion Criteria
1 Recent MI or stroke 2 NYHA class III or IV or last known left ventricular ejection fraction 30 3 Known hemorrhagic stroke at any time 4 Uncontrolled or recurrent ventricular tachycardia 5 Planned or expected cardiac surgery or revascularization within 3 months after randomization 6 Uncontrolled hypertension sitting systolic blood pressure SBP 180 mmHg or diastolic BP DBP 110 mmHg 7 Prior use of PCSK9 inhibition treatment other than evolocumab or use of evolocumab 12 weeks prior to final lipid screening 8 Untreated or inadequately treated hyperthyroidism or hypothyroidism thyroid stimulating hormone TSH lower limit of normal or 15 times the upper limit of normal and free thyroxine T4 levels that are outside normal range at final screening 9 Severe renal graft dysfunctionestimated glomerular filtration rate eGFR 20 mLmin173m2 at final screening 10 Active liver disease or hepatic dysfunction defined as aspartate aminotransferase AST or alanine aminotransferase ALT 3 times the ULN as determined by central laboratory analysis at final screening 11 Personal or family history of hereditary muscular disorders 12 Malignancy or HIV patients 13 Known major active infection or major hematologic metabolic gastrointestinal or endocrine dysfunction in the judgment of the investigator 13 Female subject who has either 1 not used acceptable methods of birth control for at least 1 month prior to screening or 2 is not willing to use such a method during treatment with IP and for an additional 15 weeks after the end of treatment with IP unless the subject is sterilized or postmenopausal 23 Known sensitivity to any of the active substances or their excipients to be administered during dosing
Methods
The baseline characteristics of the patients in the two groups will be collected with special stress on demographic data history of myocardial infarction history of previous non-hemorrhagic stroke and symptomatic peripheral artery disease At baseline all patients will be on statin therapy defined in accordance with American College of Cardiology and American Heart Association joint guidelines12 and or ezetimibe All antihypertensive medications antiplatelet and diuretic therapy will be recorded The duration of follow-up will be 12 months
Randomization
Eligible patients will be randomly assigned in a 11 ratio to receive subcutaneous injections of evolocumab either 140 mg every 2 weeks or matching placebo Randomization will be performed in a double-blinded manner with the use of a central computerized system with stratification according to the final screening LDL cholesterol level 22 or 22 mmol per liter and region
Follow up
All patients will be followed up in Hamed Al-Essa organ transplant center clinics at least every 2 months or according the local follow up protocol Patients who have a fasting LDL cholesterol level of 18 mmol per liter or higher or a non-high-density lipoprotein HDL cholesterol level of 26 mmol per liter or higher while they were taking an optimized regimen of lipid-lowering therapy which was defined as preferably a high intensity statin but must have been at least atorvastatin at a dose of 20 mg daily with or without ezetimibe
Our immunosuppression protocol consists of 5 doses of antithymocyte globulin Sanofi US Bridgewater NJ USA for high risk patients as re-transplants prior pregnancy blood transfusion HLA-antibody positive and or more than 4 HLA mismatchesor 2 doses of IL-2 receptor blocker basiliximab Novartis Inc Switzerland for low risk patients Maintenance therapy consists of prednisolone MMF and a calcineurin inhibitor CNI The dose of CNI will be gradually decreasing till the lowest dose by the end of the 1st year guided by 12-hour trough level We keep the cyclosporine A level between 200 to 250 ngml during 1st month then between 150-200 ngml for a couple of months then between 125-150 ngml for 2 months and from 75-125 ngml till the end of the 1st year Similarly we keep tacrolimus trough levels between 8 to 10 ngml during 1st 3 months then from 5-8 ngml thereafter Maintenance immunosuppression with sirolimus based regimen will be used to rejection free patients with low immunological risk after 3 months of transplantation
Acute cellular rejection ACR will be treated with intravenous methylprednisolone sodium succinate solumedrol 1 gram daily for 3 days and or thymoglobulin 1 mg kg for 7 -10 days for steroid resistant rejection Antibody mediated rejection AAMR will be treated with plasma exchange IVIG 2gmkg and rituximab Patients who will receive thymoglobulin as antirejection will be managed by secondary prophylaxis for 1 month Patients will be monitored daily during hospital stay then at each outpatient visit with complete blood picture serum creatinine creatinine clearance liver function tests bilirubin liver enzymes and albumin and drug levels
Lipid Data
The LDL cholesterol level will be checked in the central laboratory for all patients in both groups at baseline according to routine laboratory analysis and every third month using desktop Mission CE0123 cholesterol monitoring machine till the end of the study
End Points
The primary efficacy end point will be any major cardiovascular events defined as the cardiovascular death myocardial infarction stroke hospitalization for unstable angina or coronary revascularization The key secondary efficacy end point will be cardiovascular death myocardial infarction or stroke Safety was assessed through collection of data on adverse events and central laboratory testing in Ibn Sina laboratory Sabah area of Kuwait
Statistics and sample size calculation
Statistical analysis of data will be evaluated on computer using SPSS Statistical Package for Social Science for Windows 110 package software SPSS Inc Chicago IL USA In order to analyze the identifying and disease related characteristics of patients matched t-test will be used to compare means and standard deviations of numerical variables of the two groups and to test whether there will be a difference between pre-education and post-education score averages Categorical data will be compared using the chi square test Values for P less than 05 were considered significant
Confidentiality and consent
To maintain confidentiality all research data blood andurine specimens Consent Forms Data Collection Forms reports and other records that leave the site will be identified only by a Code Number-participant identification number Participant ID All records will be kept in a locked file cabinet All computer entry and networking programs will be done using PIDs only Participants identifiable private information will not be released to a third party without written permission of the participants
Detailed information will be delivered to each patient about the study including the aim and benefits Before starting the enrolment of each patient the investigator will get signed informed consent which will be kept in patient file Moreover a copy of this consent will be given to the patient
We will exclude participants with diminished capacity such as minors and mentally retarded who cannot consent for themselves from this study
The original copy of the consent will be kept in the investigators records a copy will be given to each participant and this will be documented in the participants record
The primary investigator and co-primary investigators will be responsible for implementing the consenting process and obtaining the Informed Consent of Participants
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None