A Phase 3 interventional study of Carvedilol CR and Valsartan in Hypertension, sponsored by State University of New York at Buffalo. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-05-27.
Sponsored by State University of New York at Buffalo · Phase 3, Interventional, and Treatment
14-week single blind, double baseline, forced-titration, cross-over comparison of the cardiac benefits of Coreg CR compared to valsartan added to existing ACE inhibition
Combination drug therapy is necessary for optimal blood pressure reduction and current guidelines mandate the concomitant use of ACE inhibitors and β-blockers in most patients at significant risk for cardiovascular disease (CVD) events. There is also continuing interest in combining angiotensin receptor blockers (ARBs) with ACE inhibitors in hypertension based on the unsubstantiated belief that "more complete" renin-angiotensin system inhibition is desirable. It is more attractive physiologically to combine a long-acting β-blocker with vasodilatory actions (carvedilol CR) with an ACE inhibitor because this combination addresses more directly the two fundamental hemodynamic changes needed to reduce CVD events: lowering systolic BP (afterload) and lowering heart rate; the product of the two is a reliable surrogate for reduced cardiac work. In fact, clinical trial data suggest that there is no appreciable additional BP lowering when ARBs are added to ACE inhibitors and neither class lowers heart rate. The present proposal is designed to demonstrate the superior "cardioprotection" of carvedilol CR compared to ARB (valsartan) when each is added to background ACE inhibitor therapy. Principal dependent variables include ambulatory cardiac work (24-hour mean ambulatory systolic BP x heart rate) and laboratory stress responses (central systolic time-tension indices derived from arterial tonometry pre- and post-bicycle exercise). Secondary hemodynamic variables will define changes in flow and pressure (e.g. central systolic BP and forward and reflected pressure wave estimations).
6,689 studies on the registry are indexed under Hypertension; 965 are open to participants now.
This study's enrollment of 30 is below the median of 90 across 4,995 interventional studies indexed under Hypertension.
Browse Hypertension studies →State University of New York at Buffalo is the lead sponsor of 287 studies on the registry; 65 are open to participants now.
Of its 19 completed or terminated interventional studies of FDA-regulated products, 15 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
A subject meeting any of the following conditions will be excluded from the study:
Valsartan 160 mg daily (one week) and valsartan 320 mg daily (3 weeks) followed by carvedilol CR 20 mg daily (one week) and carvedilol CR 40 mg daily (3 weeks)
Drug: Carvedilol CR · Drug: Valsartan
carvedilol CR 20 mg daily (one week) and carvedilol CR 40 mg daily (3 weeks) followed by valsartan 160 mg daily (1 week) and valsartan 320 mg daily (3 weeks).
Drug: Carvedilol CR · Drug: Valsartan
Also known as: Coreg CR
Also known as: Diovan
Difference in Resting CTTI Between Carvedilol CR (Beta-blocker) and Valsartan (ARB) in Combination With Lisinopril.
Cardiac time-tension index (CTTI) is a refined version of the rate-pressure product (RPP, historically systolic \[S\] BP x heart rate) reported by the SphygmoCor pulse wave analysis system used in this trial. CTTI is preferable to RPP because the latter overestimates the contribution of systolic BP to cardiac work (the formula intrinsically assumes maximum SBP throughout the entire heart period \[RR interval\]). In contrast, CTTI represents cardiac work during the actual systolic time interval (STI, the period of active contraction, which is about 320 ms, inversely related to HR). Thus, CTTI = \[mean systolic BP during STI, mmHg\] x \[STI/RR\] x \[HR, beats/min\] and is expressed as "CTTI units" or as "mmHg\*beats/min". Mean resting CTTI for SBP 150, HR 60 = about 2500 units (corresponding RPP = 9000 units). In this crossover study, the principal dependent variable is the mean within-subjects difference in supine CTTI between valsartan and carvedilol CR after 4 weeks of each treatment.
Time frame: End of each treatment period (4 weeks on ARB or beta-blocker)
Heart Rate (Beats/Min)
Hemodynamic variable (cardiac rate)
Time frame: End of each treatment period (4 weeks on ARB or beta-blocker)
Stroke Volume (SV)
Hemodynamic variable (volume pumped per heart beat) in mL per beat. Clinically, SV is reported simply as mL
Time frame: End of each treatment period (4 weeks on ARB or beta-blocker)
Cardiac Output
Hemodynamic variable representing whole-body blood flow (the product of heart rate and stroke volume)
Time frame: End of each 4-week treatment period (valsartan vs. carvedilol CR)
Systemic Vascular Resistance
Hemodynamic variable measured as mean arterial pressure (mmHg) / cardiac output (L/min) \*80 in units of dyne-sec-cm\[-5\]
Time frame: End of each treatment period (4 weeks of valsartan or carvedilol CR)
Central Systolic Blood Pressure
Aortic SBP derived non-invasively from radial arterial tonometry, pulse wave analysis, and a generalized transfer function algorithm within the SphygmoCor device. Aortic SBP is different from brachial SBP and is variably lower than brachial SBP due to pulse wave transmission differences between individuals. It is expressed in mmHg.
Time frame: End of each treatment period (4 weeks of valsartan or carvedilol CR)
Study subjects were recruited by advertisement or from the practice of the PI
| Milestone | ARB First | Beta-blocker First |
|---|---|---|
| Started | 15 | 15 |
| Completed | 15 | 15 |
| Not completed | 0 | 0 |
Cardiac time-tension index (CTTI) is a refined version of the rate-pressure product (RPP, historically systolic \[S\] BP x heart rate) reported by the SphygmoCor pulse wave analysis system used in this trial. CTTI is preferable to RPP because the latter overestimates the contribution of systolic BP to cardiac work (the formula intrinsically assumes maximum SBP throughout the entire heart period \[RR interval\]). In contrast, CTTI represents cardiac work during the actual systolic time interval (STI, the period of active contraction, which is about 320 ms, inversely related to HR). Thus, CTTI = \[mean systolic BP during STI, mmHg\] x \[STI/RR\] x \[HR, beats/min\] and is expressed as "CTTI units" or as "mmHg\*beats/min". Mean resting CTTI for SBP 150, HR 60 = about 2500 units (corresponding RPP = 9000 units). In this crossover study, the principal dependent variable is the mean within-subjects difference in supine CTTI between valsartan and carvedilol CR after 4 weeks of each treatment.
| CTTI units (mmHg*beats/min) | Carvedilol CR | Valsartan |
|---|---|---|
| Difference in Resting CTTI Between Carvedilol CR (Beta-blocker) and Valsartan (ARB) in Combination With Lisinopril. | 2447 ± 547 | 2500 ± 561 |
Hemodynamic variable (cardiac rate)
| beats per minute | Lisinopril Plus Valsartan | Lisinopril Plus Carvedilol |
|---|---|---|
| Heart Rate (Beats/Min) | 75 ± 17 | 68 ± 14 |
Hemodynamic variable (volume pumped per heart beat) in mL per beat. Clinically, SV is reported simply as mL
| mL or mL/beat | Lisinopril Plus Valsartan | Lisinopril Plus Carvedilol |
|---|---|---|
| Stroke Volume (SV) | 77 ± 17 | 76 ± 15 |
Hemodynamic variable representing whole-body blood flow (the product of heart rate and stroke volume)
| L/min | Lisinopril Plus Valsartan | Lisinopril Plus Carvedilol |
|---|---|---|
| Cardiac Output | 5.7 ± 1.4 | 5.1 ± 1.1 |
Hemodynamic variable measured as mean arterial pressure (mmHg) / cardiac output (L/min) \*80 in units of dyne-sec-cm\[-5\]
| dyne sec cm-5 | Lisinopril Plus Valsartan | Lisinopril Plus Carvedilol |
|---|---|---|
| Systemic Vascular Resistance | 1407 ± 378 | 1591 ± 410 |
Aortic SBP derived non-invasively from radial arterial tonometry, pulse wave analysis, and a generalized transfer function algorithm within the SphygmoCor device. Aortic SBP is different from brachial SBP and is variably lower than brachial SBP due to pulse wave transmission differences between individuals. It is expressed in mmHg.
| mmHg | Lisinopril Plus Valsartan | Lisinopril Plus Carvedilol |
|---|---|---|
| Central Systolic Blood Pressure | 130 ± 22 | 141 ± 25 |
Collected over 9 weeks (duration of the crossover study, including 4 weeks each of valsartan or carvedilol in random order and 1 week of follow-up). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Valsartan | — | 0/30 (0%) | 0/30 (0%) |
| Carvedilol CR | — | 0/30 (0%) | 0/30 (0%) |
Since all 30 participants will receive both drugs, the effects of the 2 drugs on the experimental endpoints will be compared by paired t-test. The 2 study arms refer to the randomization of sequential drug use (ARB first or beta-blocker first), which is designed to guard against the order (carryover) bias that might occur is the same drug sequence was used for all participants.
| Age, Categorical(Participants) | ARB First | Beta-blocker First | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 14 | 13 | 27 |
| >=65 years | 1 | 2 | 3 |
| Age, Continuous(years) | ARB First | Beta-blocker First | Total |
|---|---|---|---|
| Mean | 56 ± 9.5 | 56 ± 9.5 | 56 ± 9.5 |
| Sex: Female, Male(Participants) | ARB First | Beta-blocker First | Total |
|---|---|---|---|
| Female | 8 | 8 | 16 |
| Male | 7 | 7 | 14 |
| Region of Enrollment(participants) | ARB First | Beta-blocker First | Total |
|---|---|---|---|
| United States | 15 | 15 | 30 |
Plan to share: No
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State University of New York at Buffalo