To determine the underlying mechanisms responsible for thiazide-induced hyponatraemia and to identify (elderly) patients who are at risk of this potentially life-threatening complication.
ID
Source
Brief title
Condition
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Differences in the ADH-AQP2 ratio between patients previously admitted with
thiazide induced hyponatremia and matched controls without previous thiazide
induced hypoantremia.
Secondary outcome
Secondary endpoints are differences in prostaglandin E2 and AVPR2 expression.
Background summary
Thiazide diuretics are widely used for the treatment of hypertension. They are
effective, cheap and generally well tolerated. However, the use of thiazide
diuretics can be complicated by hyponatraemia and, when severe, can lead to
loss of consciousness, coma and even death. This complication is relatively
common in elderly female patients. Unfortunately it cannot be predicted in who,
or when, this serious complication will develop as the mechanisms resulting in
thiazide-induced hyponatraemia are unknown. Impaired free water excretion is
thought to be primarily responsible for thiazide-induced hyponatraemia.
Decreased sensitivity of osmoreceptors, activating mutations in the
ADH-receptor (AVPR2) or aquaporine-2 (AQP2) gene, decreased renal prostaglandin
availability or impaired renal sodium handling as a result of mutations in
thiazide- and amiloride-sensitive sodium channels may all be responsible for
thiazide-induced hyponatraemia. In the proposed trial we intend to elucidate
the mechanisms underlying thiazide-induced hyponatraemia with the aim to
identify patients who are at risk of this potentially fatal complication
Study objective
To determine the underlying mechanisms responsible for thiazide-induced
hyponatraemia and to identify (elderly) patients who are at risk of this
potentially life-threatening complication.
Study design
Prospective controlled interventional study
Intervention
Before the experiment starts thiazides are stopped for >6 weeks. Other blood
pressure lowering medication interfering with water en salt- handling will be
temporarily replaced. During the experiment patients and controls receive a
single dose of 50 mg hydrochlorothiazide.
Study burden and risks
All subjects will be admitted for at least 8 hours, allowed free access to
water and provided 3 standard meals. Patient characteristics, blood and urine
tests are taken at screening six weeks priot to the experiment, baseline and
repeated at 4, 8 and 24 hours after a single dose of hydrochlorothiazide 50 mg.
These risk are considered low because of the short duration of the wash-out
period, the close monitoring of study participants with predefined criteria and
the low cardiovascular risk of participating individuals. Thiazides and other
BP lowering drugs interfering with water- and salt handling are stopped >6
weeks before the experiment and, if necessary (BP >160/100 mmHg), replaced by a
peripheral alpha blocking agent or calcium-antagonist.
Meibergdreef 9
1105 AZ
Nederland
Meibergdreef 9
1105 AZ
Nederland
Listed location countries
Age
Inclusion criteria
Age 60-80 years
Previously admitted with thiazide-induced hyponatraemia
Patients must be willing and medically able to discontinue anti-hypertensive therapy six weeks before the study and for the duration of the study
Patients must be willing to be admitted for at least 8 hours and must be medically able to take the study medication (one tablet of hydrochlorothiazide 50 mg).
Patients must be willing to give informed consent.
Exclusion criteria
Other causes for hyponatraemia (e.g. heart failure, pulmonary disease, medication associated with hyponatraemia).;- Renal dysfunction (estimated clearance <50 ml/min according to Cockroft-Gault)
- Liver cirrhosis
- Use of beta-blocking agents for coronary disease
- Heart failure
- Allergy for sulfonamide-derivatives
- Therapy resistant hypertension (BP>140/90 mmHg while using 3 or more anti-hypertensive drugs)
-stage II hypertension or higher while using 2 anti-hypertensive drugs (BP > 160/100))
-uncontrolled hypertension (BP > 180/110))
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-004325-23-NL |
| ISRCTN | ISRCTN38727701 |
| CCMO | NL18199.018.07 |