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Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019 (REPLACECOVID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04338009
Recruitment Status : Completed
First Posted : April 8, 2020
Results First Posted : April 9, 2021
Last Update Posted : April 9, 2021
Sponsor:
Collaborators:
Jordana B. Cohen, MD, MSCE
Thomas C. Hanff, MD, MPH
University of Arizona
Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru
Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru
Hypertension Unit, Department of Pathology, Hospital Español de Mendoza, National University of Cuyo, IMBECU-CONICET, Mendoza, Argentina
Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA
Division of Infectious Diseases, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara, Mexico
Universidad Católica de Buenos Aires, Buenos Aires, Argentina
Departamento de Medicina Interna, Hospital Obrero number 3 Caja Nacional de Salud, Santa Cruz de la Sierra, Bolivia
Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru
Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA
Departamento de Emergencia, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru
Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina
Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
Jesse Chittams, MS
Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
Charles R Vasquez, MD
Information provided by (Responsible Party):
Julio A. Chirinos, University of Pennsylvania

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Condition COVID-19
Interventions Other: Discontinuation of ARB/ACEI
Other: Continuation of ARB/ACEI
Enrollment 152
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Discontinuation Arm Continuation Arm
Hide Arm/Group Description

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Period Title: Overall Study
Started 77 75
Completed 77 75
Not Completed 0 0
Arm/Group Title Discontinuation Arm Continuation Arm Total
Hide Arm/Group Description

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Total of all reporting groups
Overall Number of Baseline Participants 77 75 152
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Age Number Analyzed 77 participants 75 participants 152 participants
62  (12) 62  (12) 62  (12)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
Female
35
  45.5%
33
  44.0%
68
  44.7%
Male
42
  54.5%
42
  56.0%
84
  55.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
Hispanic or Latino
42
  54.5%
40
  53.3%
82
  53.9%
Not Hispanic or Latino
35
  45.5%
35
  46.7%
70
  46.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Hypertension  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
ACEI therapy (as opposed to ARB)*
38
  49.4%
25
  33.3%
63
  41.4%
Lowest recommended ACEI or ARB dose
14
  18.2%
14
  18.7%
28
  18.4%
Calcium channel blocker therapy
26
  33.8%
20
  26.7%
46
  30.3%
Diuretic therapy
21
  27.3%
25
  33.3%
46
  30.3%
β blocker therapy
14
  18.2%
11
  14.7%
25
  16.4%
Diabetes  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
Insulin Therapy
16
  20.8%
20
  26.7%
36
  23.7%
No insulin therapy
11
  14.3%
22
  29.3%
33
  21.7%
Dyslipidemia  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
32
  41.6%
34
  45.3%
66
  43.4%
Pre-existing cardiac disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
14
  18.2%
10
  13.3%
24
  15.8%
Ischemic heart disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
12
  15.6%
6
   8.0%
18
  11.8%
Heart Failure  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
3
   3.9%
3
   4.0%
6
   3.9%
Atrial fibrillation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
0
   0.0%
3
   4.0%
3
   2.0%
Previous PE or DVT   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
3
   3.9%
1
   1.3%
4
   2.6%
[1]
Measure Description: PE: pulmonary embolism DVT: deep vein thrombosis
Obstructive sleep apnea  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
10
  13.0%
7
   9.3%
17
  11.2%
Chronic pulmonary disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
17
  22.1%
9
  12.0%
26
  17.1%
Current Smoker  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
8
  10.4%
5
   6.7%
13
   8.6%
Illicit drug use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
3
   3.9%
2
   2.7%
5
   3.3%
Dyspnoea  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
66
  85.7%
66
  88.0%
132
  86.8%
Cough  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
58
  75.3%
59
  78.7%
117
  77.0%
Multifocal infiltrates on chest x-ray or CT  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
43
  55.8%
48
  64.0%
91
  59.9%
Oxygen saturation   [1] 
Mean (Standard Deviation)
Unit of measure:  % of oxygen in blood
Number Analyzed 77 participants 75 participants 152 participants
92  (5) 92  (8) 92  (7)
[1]
Measure Description: Taken with pulse oximeter, usually affixed onto right index finger. Measures the amount of oxygen in a subject's blood. A higher percentage is preferred.
Oxygen supplementation   [1] 
Measure Type: Number
Unit of measure:  Number of subjects requiring extra O2
Number Analyzed 77 participants 75 participants 152 participants
60 63 61
[1]
Measure Description: Refers to the number of subjects requiring supplemental oxygen (given to maintain adequate levels of blood oxygenation).
Systolic BP  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 77 participants 75 participants 152 participants
133  (22) 129  (19) 131  (20)
Diastolic BP  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 77 participants 75 participants 152 participants
77  (12) 75  (13) 76  (12)
Heart rate  
Mean (Standard Deviation)
Unit of measure:  Bpm
Number Analyzed 77 participants 75 participants 152 participants
92  (17) 91  (16) 91  (16)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 77 participants 75 participants 152 participants
33  (9) 33  (7) 33  (8)
eGFR  
Mean (Standard Deviation)
Unit of measure:  mL/min/1.73m^2
Number Analyzed 77 participants 75 participants 152 participants
81  (25) 83  (23) 82  (24)
K Serum   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 77 participants 75 participants 152 participants
4  (0.5) 4  (0.5) 4  (0.5)
[1]
Measure Description:

K: potassium measured from subject's serum

Normal levels range from 3.5-5.0 mmol/L

Leukocyte count  
Mean (Standard Deviation)
Unit of measure:  10^9 cells/L
Number Analyzed 77 participants 75 participants 152 participants
8.9  (4.5) 9.3  (4.3) 9.1  (4.4)
Platelets  
Mean (Standard Deviation)
Unit of measure:  10^3 cells/microL
Number Analyzed 77 participants 75 participants 152 participants
238  (130) 239  (109) 238  (119)
C reactive protein  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 77 participants 75 participants 152 participants
45  (77) 48  (68) 46  (72)
Days from admission to randomization  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 77 participants 75 participants 152 participants
1.5  (0.5) 1.6  (0.9) 1.5  (0.7)
Days from symptom onset to randomization  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 77 participants 75 participants 152 participants
6.8  (2.5) 6.5  (2.3) 6.65  (2.4)
1.Primary Outcome
Title Hierarchical Composite Endpoint
Hide Description

The primary endpoint of the trial will be a global rank based on patient outcomes according to four factors: (1) time to death, (2) the number of days supported by invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), (3) the number of days supported by renal replacement therapy or pressor/inotropic therapy, and (4) a modified sequential Organ Failure Assessment (SOFA) score. The modified SOFA score will include the cardiac, respiratory, renal and coagulation domains of the SOFA score.

How to interpret the rank?: patients are ranked from worst to best outcomes, such that patients with bad outcomes are ranked at the top and patients who have the best outcomes are ranked at the bottom.

Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Discontinuation Arm Continuation Arm
Hide Arm/Group Description:

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Overall Number of Participants Analyzed 77 75
Median (Inter-Quartile Range)
Unit of Measure: score on a scale (range 1 to 152)
81
(38 to 117)
73
(40 to 110)
2.Secondary Outcome
Title All-Cause Death
Hide Description [Not Specified]
Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Discontinuation Arm Continuation Arm
Hide Arm/Group Description:

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Overall Number of Participants Analyzed 77 75
Measure Type: Count of Participants
Unit of Measure: Participants
10
  13.0%
11
  14.7%
3.Secondary Outcome
Title Length of Hospital Stay
Hide Description This outcome measurement looked at the median length of hospitalization.
Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Discontinuation Arm Continuation Arm
Hide Arm/Group Description:

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Overall Number of Participants Analyzed 77 75
Median (Inter-Quartile Range)
Unit of Measure: days
5
(3 to 10)
6
(3 to 11)
4.Secondary Outcome
Title Length of ICU Stay, Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation
Hide Description [Not Specified]
Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Discontinuation Arm Continuation Arm
Hide Arm/Group Description:

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Overall Number of Participants Analyzed 77 75
Median (Inter-Quartile Range)
Unit of Measure: days
15
(6 to 27)
13
(6 to 17)
5.Secondary Outcome
Title AUC SOFA
Hide Description

The Area Under the Curve of the modified SOFA (AUC SOFA) from daily measurements, weighted to account for the shorter observation period among patients who die in-hospital.

How to interpret the AUC SOFA?: a higher area indicates more severe disease and/or longer hospitalization.The range is 0.1 to 377.3.

Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Discontinuation Arm Continuation Arm
Hide Arm/Group Description:

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Overall Number of Participants Analyzed 77 75
Median (Inter-Quartile Range)
Unit of Measure: units on a scale (SOFA x days)
7
(2 to 20)
12
(3 to 23)
6.Other Pre-specified Outcome
Title Intensive Care Unit Admission or Respiratory Failure Requiring Mechanical Ventilation.
Hide Description Need to be transferred to an intensive care unit or to supported by a breathing machine
Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Discontinuation Arm Continuation Arm
Hide Arm/Group Description:

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Overall Number of Participants Analyzed 77 75
Measure Type: Count of Participants
Unit of Measure: Participants
14
  18.2%
16
  21.3%
7.Other Pre-specified Outcome
Title Hypotension Requiring Vasopressors, Inotropes or Mechanical Hemodynamic Support
Hide Description Hypotension Requiring Vasopressors, inotropes or mechanical hemodynamic support (ventricular assist device or intra-aortic balloon pump).
Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Discontinuation Arm Continuation Arm
Hide Arm/Group Description:

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

Overall Number of Participants Analyzed 77 75
Measure Type: Count of Participants
Unit of Measure: Participants
8
  10.4%
9
  12.0%
Time Frame until hospital discharge or up to 28 days if participant were discharged prior to this time point
Adverse Event Reporting Description

The research team kept a log of all adverse events in the trial. A medically-qualified investigator assessed all AEs.

The definition of adverse events and Serious Adverse Events (SAE) is presented in detail in the study protocol, available in this clinicaltrials.gov record (protocol sections 5.2 and 5.3)

 
Arm/Group Title Discontinuation Arm Continuation Arm
Hide Arm/Group Description

The randomized intervention will be the discontinuation of ACEI/ARBs

Discontinuation of ARB/ACEI: The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.

The randomized intervention will be the continuation of ACEI/ARBs

Continuation of ARB/ACEI: The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).

All-Cause Mortality
Discontinuation Arm Continuation Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   10/77 (12.99%)   11/75 (14.67%) 
Hide Serious Adverse Events
Discontinuation Arm Continuation Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   28/77 (36.36%)   29/75 (38.67%) 
Cardiac disorders     
New or worsening congestive heart failure   1/77 (1.30%)  2/75 (2.67%) 
Myocarditis   2/77 (2.60%)  1/75 (1.33%) 
Acute myocardial infarction   0/77 (0.00%)  1/75 (1.33%) 
Acute arrhythmia   3/77 (3.90%)  6/75 (8.00%) 
General disorders     
ICU transfer   14/77 (18.18%)  16/75 (21.33%) 
All-cause death   10/77 (12.99%)  11/75 (14.67%) 
Investigations     
Delirium or encephalopathy   8/77 (10.39%)  2/75 (2.67%) 
Renal and urinary disorders     
Acute kidney injury, defined as >2-fold increase in creatinine   3/77 (3.90%)  3/75 (4.00%) 
Acute kidney injury requiring renal replacement therapy   1/77 (1.30%)  2/75 (2.67%) 
Respiratory, thoracic and mediastinal disorders     
Invasive mechanical ventilation   8/77 (10.39%)  10/75 (13.33%) 
Worsening dyspnoea or acute respiratory distress syndrome   13/77 (16.88%)  17/75 (22.67%) 
Vascular disorders     
Pulmonary embolism or deep vein thrombosis   1/77 (1.30%)  4/75 (5.33%) 
Hypotension requiring hemodynamic support   8/77 (10.39%)  9/75 (12.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Discontinuation Arm Continuation Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   0/77 (0.00%)   0/75 (0.00%) 
Limitations of the study include (1) small sample size; (2) we did not control participant ACEI or ARB dosing or other medication exposures during the trial; (3) Although outcome adjudicators were masked to the randomly assigned groups when determining clinical endpoints, providers caring for the patients were aware of the group the patient was assigned to. It is possible that the open-label nature of the study might have introduced information bias or influenced provider behavior.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Jordana Cohen
Organization: University of Pennsylvania
Phone: 215-662-4000
EMail: jco@pennmedicine.upenn.edu
Publications:
Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, Alexander L, Estep K, Hassen Abate K, Akinyemiju TF, Ali R, Alvis-Guzman N, Azzopardi P, Banerjee A, Bärnighausen T, Basu A, Bekele T, Bennett DA, Biadgilign S, Catalá-López F, Feigin VL, Fernandes JC, Fischer F, Gebru AA, Gona P, Gupta R, Hankey GJ, Jonas JB, Judd SE, Khang YH, Khosravi A, Kim YJ, Kimokoti RW, Kokubo Y, Kolte D, Lopez A, Lotufo PA, Malekzadeh R, Melaku YA, Mensah GA, Misganaw A, Mokdad AH, Moran AE, Nawaz H, Neal B, Ngalesoni FN, Ohkubo T, Pourmalek F, Rafay A, Rai RK, Rojas-Rueda D, Sampson UK, Santos IS, Sawhney M, Schutte AE, Sepanlou SG, Shifa GT, Shiue I, Tedla BA, Thrift AG, Tonelli M, Truelsen T, Tsilimparis N, Ukwaja KN, Uthman OA, Vasankari T, Venketasubramanian N, Vlassov VV, Vos T, Westerman R, Yan LL, Yano Y, Yonemoto N, Zaki ME, Murray CJ. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA. 2017 Jan 10;317(2):165-182. doi: 10.1001/jama.2016.19043. Erratum in: JAMA. 2017 Feb 14;317(6):648.
Chow SC, Shao J, Wang H. Sample Size Calculations in Clinical Research. 2nd Edition ed. New York: Dekker; 2008.
PASS 16 Power Analysis and Sample Size Software. NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass. 2018.
Therneau TM, Grambsch PM. Modeling Survival Data: Extending the Cox Model. In: Statistics for Biology and Health. New York, NY: Springer; 2001.
Little RJ. Modeling the drop-out mechanism in repeated-measures studies. Journal of the American Statistical Association. 1995;90:1112-1121.
Layout table for additonal information
Responsible Party: Julio A. Chirinos, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT04338009    
Other Study ID Numbers: 842810
First Submitted: April 1, 2020
First Posted: April 8, 2020
Results First Submitted: January 28, 2021
Results First Posted: April 9, 2021
Last Update Posted: April 9, 2021