Trial Outcomes & Findings for Cardioprotective Benefits of Carvedilol-CR or Valsartan Added to Lisinopril (NCT NCT00657241)
NCT ID: NCT00657241
Last Updated: 2022-05-27
Results Overview
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.
COMPLETED
PHASE3
30 participants
End of each treatment period (4 weeks on ARB or beta-blocker)
2022-05-27
Participant Flow
Study subjects were recruited by advertisement or from the practice of the PI
Prior antihypertensive medications were discontinued and subjects entered a 3-week run-in taking lisinopril 40 mg daily
Participant milestones
| Measure |
ARB First
Lisinopril 40 mg daily plus valsartan 160 mg daily (one week) then valsartan 320 mg daily (3 weeks) followed by lisinopril 40 mg daily plus carvedilol CR 20 mg daily (one week) then carvedilol CR 40 mg daily (3 weeks)
|
Beta-blocker First
Lisinopril 40 mg daily plus carvedilol CR 20 mg (one week) and carvedilol CR 40 mg (3 weeks) followed by lisinopril 40 mg daily plus valsartan 160 mg daily (one week) and valsartan 320 mg daily (3 weeks).
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
COMPLETED
|
15
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cardioprotective Benefits of Carvedilol-CR or Valsartan Added to Lisinopril
Baseline characteristics by cohort
| Measure |
ARB First
n=15 Participants
Lisinopril 40 mg daily plus valsartan 160 mg daily (one week) then valsartan 320 mg daily (3 weeks) followed by lisinopril 40 mg daily plus carvedilol CR 20 mg daily (1 week) then carvedilol CR 40 mg daily (3 weeks)
|
Beta-blocker First
n=15 Participants
Lisinopril 40 mg daily plus carvedilol CR 20 mg daily (1 week) then carvedilol CR 40 mg daily (3 weeks) followed by lisinopril 40 mg daily plus valsartan 160 mg daily (one week) then valsartan 320 mg daily (3 weeks)
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Age, Continuous
|
56 years
STANDARD_DEVIATION 9.5 • n=99 Participants
|
56 years
STANDARD_DEVIATION 9.5 • n=107 Participants
|
56 years
STANDARD_DEVIATION 9.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=99 Participants
|
15 participants
n=107 Participants
|
30 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: End of each treatment period (4 weeks on ARB or beta-blocker)Population: Analysis groups are different from treatment arms, which reflect the sequence of administration of the comparators, valsartan or carvedilol CR, which are received by all participants. CTTI comparisons made at end of each 4-week treatment period; study powered to detect an 8% difference in CTTI by paired t-test at p \< 0.05, power 0.8.
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.
Outcome measures
| Measure |
Carvedilol CR
n=30 Participants
Lisinopril 40 mg daily plus carvedilol CR 20 mg (one week) then carvedilol CR 40 mg (3 weeks) administered first or second
|
Valsartan
n=30 Participants
lisinopril 40 mg daily plus valsartan 160 mg daily (1 week) then valsartan 320 mg daily (3 weeks) administered first or second
|
|---|---|---|
|
Difference in Resting CTTI Between Carvedilol CR (Beta-blocker) and Valsartan (ARB) in Combination With Lisinopril.
|
2447 CTTI units (mmHg*beats/min)
Standard Deviation 547
|
2500 CTTI units (mmHg*beats/min)
Standard Deviation 561
|
SECONDARY outcome
Timeframe: End of each treatment period (4 weeks on ARB or beta-blocker)Population: These analysis groups reflect the main study aim of direct comparison of ARB to beta-blocker with respect to cardiac work (CTTI). The analysis groups are not the same as the cross-over arms that represent sequence of drug administration (i.e. "ARB first" or "beta-blocker first").
Hemodynamic variable (cardiac rate)
Outcome measures
| Measure |
Carvedilol CR
n=30 Participants
Lisinopril 40 mg daily plus carvedilol CR 20 mg (one week) then carvedilol CR 40 mg (3 weeks) administered first or second
|
Valsartan
n=30 Participants
lisinopril 40 mg daily plus valsartan 160 mg daily (1 week) then valsartan 320 mg daily (3 weeks) administered first or second
|
|---|---|---|
|
Heart Rate (Beats/Min)
|
75 beats per minute
Standard Deviation 17
|
68 beats per minute
Standard Deviation 14
|
SECONDARY outcome
Timeframe: End of each treatment period (4 weeks on ARB or beta-blocker)Population: Mean of (intra-individual) SV values after 4 weeks of valsartan or carvedilol CR
Hemodynamic variable (volume pumped per heart beat) in mL per beat. Clinically, SV is reported simply as mL
Outcome measures
| Measure |
Carvedilol CR
n=30 Participants
Lisinopril 40 mg daily plus carvedilol CR 20 mg (one week) then carvedilol CR 40 mg (3 weeks) administered first or second
|
Valsartan
n=30 Participants
lisinopril 40 mg daily plus valsartan 160 mg daily (1 week) then valsartan 320 mg daily (3 weeks) administered first or second
|
|---|---|---|
|
Stroke Volume (SV)
|
77 mL or mL/beat
Standard Deviation 17
|
76 mL or mL/beat
Standard Deviation 15
|
SECONDARY outcome
Timeframe: End of each 4-week treatment period (valsartan vs. carvedilol CR)Population: 4-week treatment period (valsartan vs. carvedilol CR); comparison by paired t-test
Hemodynamic variable representing whole-body blood flow (the product of heart rate and stroke volume)
Outcome measures
| Measure |
Carvedilol CR
n=30 Participants
Lisinopril 40 mg daily plus carvedilol CR 20 mg (one week) then carvedilol CR 40 mg (3 weeks) administered first or second
|
Valsartan
n=30 Participants
lisinopril 40 mg daily plus valsartan 160 mg daily (1 week) then valsartan 320 mg daily (3 weeks) administered first or second
|
|---|---|---|
|
Cardiac Output
|
5.7 L/min
Standard Deviation 1.4
|
5.1 L/min
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: End of each treatment period (4 weeks of valsartan or carvedilol CR)Population: Valsartan vs. carvedilol CR at end of 4-week treatment period; comparison by paired t-test
Hemodynamic variable measured as mean arterial pressure (mmHg) / cardiac output (L/min) \*80 in units of dyne-sec-cm\[-5\]
Outcome measures
| Measure |
Carvedilol CR
n=30 Participants
Lisinopril 40 mg daily plus carvedilol CR 20 mg (one week) then carvedilol CR 40 mg (3 weeks) administered first or second
|
Valsartan
n=30 Participants
lisinopril 40 mg daily plus valsartan 160 mg daily (1 week) then valsartan 320 mg daily (3 weeks) administered first or second
|
|---|---|---|
|
Systemic Vascular Resistance
|
1407 dyne sec cm-5
Standard Deviation 378
|
1591 dyne sec cm-5
Standard Deviation 410
|
SECONDARY outcome
Timeframe: End of each treatment period (4 weeks of valsartan or carvedilol CR)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.
Outcome measures
| Measure |
Carvedilol CR
n=30 Participants
Lisinopril 40 mg daily plus carvedilol CR 20 mg (one week) then carvedilol CR 40 mg (3 weeks) administered first or second
|
Valsartan
n=30 Participants
lisinopril 40 mg daily plus valsartan 160 mg daily (1 week) then valsartan 320 mg daily (3 weeks) administered first or second
|
|---|---|---|
|
Central Systolic Blood Pressure
|
130 mmHg
Standard Deviation 22
|
141 mmHg
Standard Deviation 25
|
Adverse Events
Valsartan
Carvedilol CR
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place