Trial Outcomes & Findings for HALT Progression of Polycystic Kidney Disease Study A (NCT NCT00283686)

Last Updated: 2020-04-21

Results Overview

Annual percentage change in total kidney volume as assessed by abdominal magnetic resonance imaging (MRI) at baseline, 2 years, 4 years, and 5 years follow-up.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

558 participants

Primary outcome timeframe

Baseline and 2-, 4- and 5-year follow-up

Results posted on

2020-04-21

Participant Flow

Participants were enrolled at seven clinical sites between February 2006 and June 2009.

Participant milestones

Participant milestones
Measure	ACE-I/ARB and Standard BP ACE-I + angiotensin-receptor blocker (ARB) and standard blood pressure control of 120-130/70-80 mm Hg Lisinopril and Telmisartan: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 120-130/70-80 mm Hg.	ACE-I/ARB and Low BP ACE-I + angiotensin-receptor blocker (ARB) and low blood pressure control of 95-110/60-75 mm Hg Lisinopril and Telmisartan: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve low blood pressure control of 95-110/60-75 mm Hg.	ACE-I/Placebo and Standard BP ACE-I + Placebo and standard blood pressure control of 120-130/70-80 mm Hg Lisinopril and Placebo: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 120-130/70-80 mm Hg.	ACE-I/Placebo and Low BP ACE-I + Placebo and low blood pressure control of 95-110/60-75 mm Hg Lisinopril and Placebo: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve low blood pressure control of 95-110/60-75 mm Hg.
Overall Study STARTED	140	133	144	141
Overall Study COMPLETED	111	92	111	109
Overall Study NOT COMPLETED	29	41	33	32

Reasons for withdrawal

Reasons for withdrawal
Measure	ACE-I/ARB and Standard BP ACE-I + angiotensin-receptor blocker (ARB) and standard blood pressure control of 120-130/70-80 mm Hg Lisinopril and Telmisartan: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 120-130/70-80 mm Hg.	ACE-I/ARB and Low BP ACE-I + angiotensin-receptor blocker (ARB) and low blood pressure control of 95-110/60-75 mm Hg Lisinopril and Telmisartan: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve low blood pressure control of 95-110/60-75 mm Hg.	ACE-I/Placebo and Standard BP ACE-I + Placebo and standard blood pressure control of 120-130/70-80 mm Hg Lisinopril and Placebo: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 120-130/70-80 mm Hg.	ACE-I/Placebo and Low BP ACE-I + Placebo and low blood pressure control of 95-110/60-75 mm Hg Lisinopril and Placebo: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve low blood pressure control of 95-110/60-75 mm Hg.
Overall Study Death	1	1	1	0
Overall Study Lost to Follow-up	21	31	26	20
Overall Study Less than full participation	7	9	6	12

Baseline Characteristics

HALT Progression of Polycystic Kidney Disease Study A

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ACE-I/ARB and Standard BP n=140 Participants ACE-I + ARB and standard blood pressure control of 120-130/70-80 mm Hg Lisinopril and Telmisartan: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 120-130/70-80 mm Hg.	ACE-I/ARB and Low BP n=133 Participants ACE-I + ARB and low blood pressure control of 95-110/60-75 mm Hg Lisinopril and Telmisartan: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve low blood pressure control of 95-110/60-75 mm Hg.	ACE-I/Placebo and Standard BP n=144 Participants ACE-I + Placebo and standard blood pressure control of 120-130/70-80 mm Hg Lisinopril and Placebo: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 120-130/70-80 mm Hg.	ACE-I/Placebo and Low BP n=141 Participants ACE-I + Placebo and low blood pressure control of 95-110/60-75 mm Hg Lisinopril and Placebo: Lisinopril titrated to 5mg, 10mg, 20mg, 40mg and placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve low blood pressure control of 95-110/60-75 mm Hg.	Total n=558 Participants Total of all reporting groups
Age, Continuous	37.0 years STANDARD_DEVIATION 8.3 • n=5 Participants	37.1 years STANDARD_DEVIATION 8.4 • n=7 Participants	35.8 years STANDARD_DEVIATION 8.6 • n=5 Participants	36.8 years STANDARD_DEVIATION 8.0 • n=4 Participants	36.7 years STANDARD_DEVIATION 8.3 • n=21 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	64 Participants n=7 Participants	73 Participants n=5 Participants	70 Participants n=4 Participants	275 Participants n=21 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	69 Participants n=7 Participants	71 Participants n=5 Participants	71 Participants n=4 Participants	283 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	14 Participants n=21 Participants
Race (NIH/OMB) White	127 Participants n=5 Participants	128 Participants n=7 Participants	131 Participants n=5 Participants	131 Participants n=4 Participants	517 Participants n=21 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=4 Participants	15 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Age at Diagnosis of autosomal dominant polycystic kidney disease (ADPKD)	27.2 years STANDARD_DEVIATION 10.0 • n=5 Participants	28.5 years STANDARD_DEVIATION 10.0 • n=7 Participants	27.0 years STANDARD_DEVIATION 9.5 • n=5 Participants	27.6 years STANDARD_DEVIATION 10.4 • n=4 Participants	27.6 years STANDARD_DEVIATION 10.0 • n=21 Participants
Body Mass Index (kg/m2)	27.4 kg/m2 STANDARD_DEVIATION 5.4 • n=5 Participants	27.4 kg/m2 STANDARD_DEVIATION 5.1 • n=7 Participants	27.3 kg/m2 STANDARD_DEVIATION 5.5 • n=5 Participants	26.8 kg/m2 STANDARD_DEVIATION 4.8 • n=4 Participants	27.2 kg/m2 STANDARD_DEVIATION 5.2 • n=21 Participants
Serum Creatinine (mg/dl)	1.0 mg/dl STANDARD_DEVIATION 0.3 • n=5 Participants	1.0 mg/dl STANDARD_DEVIATION 0.2 • n=7 Participants	0.9 mg/dl STANDARD_DEVIATION 0.2 • n=5 Participants	1.0 mg/dl STANDARD_DEVIATION 0.2 • n=4 Participants	1.0 mg/dl STANDARD_DEVIATION 0.2 • n=21 Participants
Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) eGFR (ml/min/m2)	88.5 ml/min/m2 STANDARD_DEVIATION 18.8 • n=5 Participants	86.5 ml/min/m2 STANDARD_DEVIATION 19.3 • n=7 Participants	92.9 ml/min/m2 STANDARD_DEVIATION 18.5 • n=5 Participants	87.6 ml/min/m2 STANDARD_DEVIATION 17.2 • n=4 Participants	88.9 ml/min/m2 STANDARD_DEVIATION 18.5 • n=21 Participants
PKD Genotype PKD1	103 participants n=5 Participants	87 participants n=7 Participants	101 participants n=5 Participants	91 participants n=4 Participants	382 participants n=21 Participants
PKD Genotype PKD2	15 participants n=5 Participants	27 participants n=7 Participants	19 participants n=5 Participants	23 participants n=4 Participants	84 participants n=21 Participants
PKD Genotype No Mutation Detected	10 participants n=5 Participants	10 participants n=7 Participants	12 participants n=5 Participants	14 participants n=4 Participants	46 participants n=21 Participants
PKD Genotype No information	12 participants n=5 Participants	9 participants n=7 Participants	12 participants n=5 Participants	13 participants n=4 Participants	46 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and 2-, 4- and 5-year follow-up

Population: Analyses were conducted on all participants who had at least one total kidney volume measurement using intention to treat.

Annual percentage change in total kidney volume as assessed by abdominal magnetic resonance imaging (MRI) at baseline, 2 years, 4 years, and 5 years follow-up.

Outcome measures

Outcome measures
Measure	ACE-I + ARB n=271 Participants ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=282 Participants ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=271 Participants Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=282 Participants Targeted blood pressure was 120/70 to 130/80 mm Hg
Study A: Percent Annual Change in Total Kidney Volume	6.0 percentage of Total Kidney Volume Interval 5.5 to 6.4	6.2 percentage of Total Kidney Volume Interval 5.7 to 6.7	5.6 percentage of Total Kidney Volume Interval 5.2 to 6.1	6.6 percentage of Total Kidney Volume Interval 6.1 to 7.1

SECONDARY outcome

Timeframe: Up to 96 months (6 month assessments)

Population: Analyses were intention to treat: All participants who were randomized.

The estimated GFR was calculated by means of the Chronic Kidney Disease Epidemiology Collaboration equation with the use of central serum creatinine measurements.

Outcome measures

Outcome measures
Measure	ACE-I + ARB n=273 Participants ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=284 Participants ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=274 Participants Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=283 Participants Targeted blood pressure was 120/70 to 130/80 mm Hg
Kidney Function (eGFR)	-3.0 ml/min/1.73/m2/yr Interval -3.3 to -2.7	-2.9 ml/min/1.73/m2/yr Interval -3.2 to -2.6	-2.9 ml/min/1.73/m2/yr Interval -3.2 to -2.6	-3.0 ml/min/1.73/m2/yr Interval -3.3 to -2.7

SECONDARY outcome

Timeframe: Up to 96 months (assessed annually)

Population: Analysis by intention to treat

Urine albumin excretion, centrally processed from 24 hour urine collection

Outcome measures

Outcome measures
Measure	ACE-I + ARB n=273 Participants ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=284 Participants ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=274 Participants Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=283 Participants Targeted blood pressure was 120/70 to 130/80 mm Hg
Albuminuria	-1.1 annual percent change in mg/24 hr Interval -3.1 to 0.8	-0.4 annual percent change in mg/24 hr Interval -2.3 to 1.6	-3.8 annual percent change in mg/24 hr Interval -5.7 to -1.8	2.4 annual percent change in mg/24 hr Interval 0.5 to 4.4

SECONDARY outcome

Timeframe: Up to 96 months (assessed annually)

Population: Analysis using intention to treat

Urinary aldosterone excretion, centrally processed, 24 hour urine collection

Outcome measures

Outcome measures
Measure	ACE-I + ARB n=273 Participants ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=284 Participants ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=274 Participants Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=283 Participants Targeted blood pressure was 120/70 to 130/80 mm Hg
Aldosterone	-8.5 annual % change micrograms per 24 hr Interval -9.9 to -7.2	-7.3 annual % change micrograms per 24 hr Interval -8.7 to -5.9	-8.5 annual % change micrograms per 24 hr Interval -9.9 to -7.1	-7.3 annual % change micrograms per 24 hr Interval -8.6 to -5.9

SECONDARY outcome

Timeframe: 0, 24 months, 48 months, 60 months

Population: Analyses were conducted using intention to treat for participants with at least one left ventricular mass index measure.

Left ventricular mass index (g/m\^2) measured by MRI, centrally reviewed and measured

Outcome measures

Outcome measures
Measure	ACE-I + ARB n=268 Participants ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=274 Participants ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=265 Participants Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=277 Participants Targeted blood pressure was 120/70 to 130/80 mm Hg
Left Ventricular Mass Index	-0.91 annual change in g/m^2 Interval -1.15 to -0.68	-0.83 annual change in g/m^2 Interval -1.06 to -0.59	-1.17 annual change in g/m^2 Interval -1.41 to -0.93	-0.57 annual change in g/m^2 Interval -0.8 to -0.34

SECONDARY outcome

Timeframe: 0, 24 months, 48 months, 60 months

Population: Analyses were conducted using intention to treat analyses for participants with at least one valid renal blood flow measure.

renal blood flow (mL/min/1.73 m\^2) from MRI, centrally reviewed and measured. This outcome was more difficult to measure resulting in more missing data than other MRI outcomes such as total kidney volume (TKV) and left ventricular mass index (LVMI).

Outcome measures

Outcome measures
Measure	ACE-I + ARB n=233 Participants ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=247 Participants ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=236 Participants Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=244 Participants Targeted blood pressure was 120/70 to 130/80 mm Hg
Renal Blood Flow	-6.6 annual change in mL/min/1.73 m^2 Interval -11.0 to -2.1	-9.5 annual change in mL/min/1.73 m^2 Interval -14.0 to -5.1	-7.6 annual change in mL/min/1.73 m^2 Interval -12.0 to -3.1	-8.5 annual change in mL/min/1.73 m^2 Interval -13.0 to -4.1

SECONDARY outcome

Timeframe: Up to 96 months

Population: Intention to treat analysis: All participants who were randomized.

Outcome measures

Outcome measures
Measure	ACE-I + ARB n=273 Participants ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=285 Participants ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=274 Participants Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=284 Participants Targeted blood pressure was 120/70 to 130/80 mm Hg
All-Cause Hospitalizations	85 events	128 events	93 events	120 events

SECONDARY outcome

Timeframe: baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually)

Population: Analysis using intention to treat

Short Form-36 Quality of Life Physical Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)

Outcome measures

Outcome measures
Measure	ACE-I + ARB n=273 Participants ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=285 Participants ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=274 Participants Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=284 Participants Targeted blood pressure was 120/70 to 130/80 mm Hg
Quality of Life Physical Component Summary	-0.24 annual change in units on a scale Interval -0.37 to -0.11	-.23 annual change in units on a scale Interval -0.35 to -0.1	-0.17 annual change in units on a scale Interval -0.3 to -0.03	-0.30 annual change in units on a scale Interval -0.43 to -0.17

SECONDARY outcome

Timeframe: baseline, 12, 24, 36, 48, 60, 72, 84, and 96 months (assessed annually)

Population: Analysis using intention to treat.

Short Form-36 Quality of LIfe Mental Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome)

Outcome measures

Outcome measures
Measure	ACE-I + ARB n=273 Participants ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=285 Participants ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=274 Participants Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=284 Participants Targeted blood pressure was 120/70 to 130/80 mm Hg
Quality of Life Mental Component Summary	0.19 annual change in units on a scale Interval 0.03 to 0.35	-0.06 annual change in units on a scale Interval -0.21 to 0.1	-0.05 annual change in units on a scale Interval -0.21 to 0.11	0.18 annual change in units on a scale Interval 0.03 to 0.33

Adverse Events

ACE-I + ARB

Serious events: 58 serious events

Other events: 23 other events

Deaths: 0 deaths

ACE-I Alone

Serious events: 90 serious events

Other events: 21 other events

Deaths: 0 deaths

Low Blood Pressure Group

Serious events: 69 serious events

Other events: 23 other events

Deaths: 0 deaths

Standard Blood Pressure Group

Serious events: 79 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	ACE-I + ARB n=273 participants at risk ACE-I plus ARB (Lisinopril plus telmisartan)	ACE-I Alone n=285 participants at risk ACE-I monotherapy (lisinopril only)	Low Blood Pressure Group n=274 participants at risk Targeted blood pressure was 95/60 to 110/75 mm Hg	Standard Blood Pressure Group n=284 participants at risk Targeted blood pressure was 120/70 to 130/80 mm Hg
Renal and urinary disorders Acute kidney injury	4.8% 13/273 • Number of events 15 • 5-8 years with average follow-up of 5.7 years	5.6% 16/285 • Number of events 19 • 5-8 years with average follow-up of 5.7 years	5.8% 16/274 • Number of events 17 • 5-8 years with average follow-up of 5.7 years	4.6% 13/284 • Number of events 17 • 5-8 years with average follow-up of 5.7 years
Metabolism and nutrition disorders Hyperkalemia	4.0% 11/273 • Number of events 13 • 5-8 years with average follow-up of 5.7 years	1.8% 5/285 • Number of events 6 • 5-8 years with average follow-up of 5.7 years	2.6% 7/274 • Number of events 8 • 5-8 years with average follow-up of 5.7 years	3.2% 9/284 • Number of events 11 • 5-8 years with average follow-up of 5.7 years

Additional Information

Dr. Arlene Chapman

Emory University

Phone: (404) 712-1993

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place