Trial Outcomes & Findings for Hydrochlorothiazide for Kidney Stone Recurrence Prevention (NCT NCT03057431)

Results Overview

Composite of symptomatic or radiological recurrences, defined as either a symptomatic kidney stone passage or radiological kidney stone recurrence on CT. Symptomatic recurrence was defined as the visible passage of a stone with or without accompanying typical symptoms (such as flank or loin pain and hematuria) or as the presence of a symptomatic or asymptomatic stone that was determined to require surgical removal. If a patient had symptoms during the trial that were suggestive of a possible stone passage but no visible stone had been observed, local investigators evaluated the symptoms of the patient and judged whether a stone passage had occurred. Radiological recurrence was defined as a new stone formed or enlargement of a preexisting stone.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

416 participants

Primary outcome timeframe

After 3 years

Results posted on

2024-02-01

Participant Flow

Specified in the protocol

No significant events.

Participant milestones

Participant milestones
Measure	Placebo Once daily for 3 years Placebo oral capsule: Once daily for 3 years	12.5 mg Hydrochlorothiazide Once daily for 3 years 12.5 mg hydrochlorothiazide: Once daily for 3 years	25.0 mg Hydrochlorothiazide Once daily for 3 years 25.0 mg hydrochlorothiazide: Once daily for 3 years	50.0 mg Hydrochlorothiazide Once daily for 3 years 50.0 mg hydrochlorothiazide: Once daily for 3 years
Overall Study STARTED	102	105	108	101
Overall Study COMPLETED	95	102	104	92
Overall Study NOT COMPLETED	7	3	4	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Hydrochlorothiazide for Kidney Stone Recurrence Prevention

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=102 Participants Once daily for 3 years Placebo oral capsule: Once daily for 3 years	12.5 mg Hydrochlorothiazide n=105 Participants Once daily for 3 years 12.5 mg hydrochlorothiazide: Once daily for 3 years	25.0 mg Hydrochlorothiazide n=108 Participants Once daily for 3 years 25.0 mg hydrochlorothiazide: Once daily for 3 years	50.0 mg Hydrochlorothiazide n=101 Participants Once daily for 3 years 50.0 mg hydrochlorothiazide: Once daily for 3 years	Total n=416 Participants Total of all reporting groups
Age, Continuous	47 years n=5 Participants	49 years n=7 Participants	48 years n=5 Participants	50 years n=4 Participants	49 years n=21 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	16 Participants n=7 Participants	22 Participants n=5 Participants	21 Participants n=4 Participants	85 Participants n=21 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	89 Participants n=7 Participants	86 Participants n=5 Participants	80 Participants n=4 Participants	331 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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
Ethnicity (NIH/OMB) Not Hispanic or Latino	102 Participants n=5 Participants	105 Participants n=7 Participants	108 Participants n=5 Participants	101 Participants n=4 Participants	416 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	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
Region of Enrollment Switzerland	102 Participants n=5 Participants	105 Participants n=7 Participants	108 Participants n=5 Participants	101 Participants n=4 Participants	416 Participants n=21 Participants

PRIMARY outcome

Timeframe: After 3 years

Population: Intention-to-treat

Composite of symptomatic or radiological recurrences, defined as either a symptomatic kidney stone passage or radiological kidney stone recurrence on CT. Symptomatic recurrence was defined as the visible passage of a stone with or without accompanying typical symptoms (such as flank or loin pain and hematuria) or as the presence of a symptomatic or asymptomatic stone that was determined to require surgical removal. If a patient had symptoms during the trial that were suggestive of a possible stone passage but no visible stone had been observed, local investigators evaluated the symptoms of the patient and judged whether a stone passage had occurred. Radiological recurrence was defined as a new stone formed or enlargement of a preexisting stone.

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants Once daily for 3 years Placebo oral capsule: Once daily for 3 years	12.5 mg Hydrochlorothiazide n=105 Participants Once daily for 3 years 12.5 mg hydrochlorothiazide: Once daily for 3 years	25.0 mg Hydrochlorothiazide n=108 Participants Once daily for 3 years 25.0 mg hydrochlorothiazide: Once daily for 3 years	50.0 mg Hydrochlorothiazide n=101 Participants Once daily for 3 years 50.0 mg hydrochlorothiazide: Once daily for 3 years
Number of Participants With Stone Recurrences	60 Participants	62 Participants	61 Participants	49 Participants

SECONDARY outcome

Timeframe: After 3 years

Population: Intention-to-treat

Symptomatic recurrence was defined as the visible passage of a stone with or without accompanying typical symptoms (such as flank or loin pain and hematuria) or as the presence of a symptomatic or asymptomatic stone that was determined to require surgical removal. If a patient had symptoms during the trial that were suggestive of a possible stone passage but no visible stone had been observed, local investigators evaluated the symptoms of the patient and judged whether a stone passage had occurred.

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants Once daily for 3 years Placebo oral capsule: Once daily for 3 years	12.5 mg Hydrochlorothiazide n=105 Participants Once daily for 3 years 12.5 mg hydrochlorothiazide: Once daily for 3 years	25.0 mg Hydrochlorothiazide n=108 Participants Once daily for 3 years 25.0 mg hydrochlorothiazide: Once daily for 3 years	50.0 mg Hydrochlorothiazide n=101 Participants Once daily for 3 years 50.0 mg hydrochlorothiazide: Once daily for 3 years
Number of Symptomatic Stone Recurrences	35 Participants	40 Participants	43 Participants	28 Participants

SECONDARY outcome

Timeframe: After 3 years

Population: Intention-to-treat

Radiological stone recurrence was defined as a new stone formed or enlargement of a preexisting stone (assessed by low-dose CT of the kidney at the end of the study compared to the low-dose CT of the kidney at the baseline visit).

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants Once daily for 3 years Placebo oral capsule: Once daily for 3 years	12.5 mg Hydrochlorothiazide n=105 Participants Once daily for 3 years 12.5 mg hydrochlorothiazide: Once daily for 3 years	25.0 mg Hydrochlorothiazide n=108 Participants Once daily for 3 years 25.0 mg hydrochlorothiazide: Once daily for 3 years	50.0 mg Hydrochlorothiazide n=101 Participants Once daily for 3 years 50.0 mg hydrochlorothiazide: Once daily for 3 years
Number of Radiologic Stone Recurrences.	46 Participants	44 Participants	32 Participants	31 Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

12.5 mg Hydrochlorothiazide

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

25.0 mg Hydrochlorothiazide

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

50.0 mg Hydrochlorothiazide

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=102 participants at risk Once daily for 3 years Placebo oral capsule: Once daily for 3 years	12.5 mg Hydrochlorothiazide n=105 participants at risk Once daily for 3 years 12.5 mg hydrochlorothiazide: Once daily for 3 years	25.0 mg Hydrochlorothiazide n=108 participants at risk Once daily for 3 years 25.0 mg hydrochlorothiazide: Once daily for 3 years	50.0 mg Hydrochlorothiazide n=101 participants at risk Once daily for 3 years 50.0 mg hydrochlorothiazide: Once daily for 3 years
Reproductive system and breast disorders Pregnancy	2.0% 2/102 • Number of events 2 • Every 3 months until study end at 3 years. We used standard definitions.	0.00% 0/105 • Every 3 months until study end at 3 years. We used standard definitions.	1.9% 2/108 • Number of events 2 • Every 3 months until study end at 3 years. We used standard definitions.	0.99% 1/101 • Number of events 1 • Every 3 months until study end at 3 years. We used standard definitions.

Other adverse events

Other adverse events
Measure	Placebo n=102 participants at risk Once daily for 3 years Placebo oral capsule: Once daily for 3 years	12.5 mg Hydrochlorothiazide n=105 participants at risk Once daily for 3 years 12.5 mg hydrochlorothiazide: Once daily for 3 years	25.0 mg Hydrochlorothiazide n=108 participants at risk Once daily for 3 years 25.0 mg hydrochlorothiazide: Once daily for 3 years	50.0 mg Hydrochlorothiazide n=101 participants at risk Once daily for 3 years 50.0 mg hydrochlorothiazide: Once daily for 3 years
Endocrine disorders New onset diabetes mellitus	0.98% 1/102 • Number of events 1 • Every 3 months until study end at 3 years. We used standard definitions.	1.9% 2/105 • Number of events 2 • Every 3 months until study end at 3 years. We used standard definitions.	6.5% 7/108 • Number of events 7 • Every 3 months until study end at 3 years. We used standard definitions.	2.0% 2/101 • Number of events 2 • Every 3 months until study end at 3 years. We used standard definitions.

Additional Information

Prof. Daniel Fuster

Inselspital, Bern University Hospital, Bern, Switzerland

Phone: ++41316323144

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place