A clinical trial to study the effect of conivaptan hydrochloride in patients with Euvolemic and Hypervolemic hyponatremia (a condition where the level of a chemical ion in blood goes below the normal levels)
Efficacy and Safety of Intravenous Administration of Conivaptan Hydrochloride in the Treatment of Euvolemic and Hypervolemic Hyponatremia - A multicentric, open label, non comparative, phase III study
1.Patients of either sex, aged more than or equal to 18 years.
2.Patients who have mean serum sodium concentration between 115 and 129 mEq per liter both inclusive.
3.Patients who have serum osmolality less 290 mOsmol per kg water.
Mean serum sodium concentration refers to the mean of two serum sodium readings 0 and 4 hours obtained during the baseline period of 4 to 12 hours. For the patients in whom treatment of hyponatremia with conivaptan cannot be delayed, the sample at 0 hr will be considered as the baseline reading.
Note: Patients of either sex, aged more than or equal to 18 years
ExclusionCriteria
Details
1.Patients unwilling or unable to give informed consent.
2.Random blood glucose more than or equal to 300 mg per dl.
3.Urinary sodium less tha 30mEq per liter with normal dietary salt intake.
4.Patients expected to have hyponatremia necessitating emergent treatment during the study.
5.Patients diagnosed with hypovolemic hyponatremia.
6.Patients diagnosed with congestive heart failure CHF NYHA class IV or Cirrhosis
7.Pregnant or lactating women or women in reproductive age group not using reliable contraception i.e. a medically accepted effective method of birth control
8.Patients with cardiac surgery, myocardial infarction, unstable angina or cerebrovascular accident in the past 3 months.
9.Patients with uncontrolled hypertension or supine systolic blood pressure less than 85 mmHg.
10.Patients with uncontrolled arrhythmias
11.Patients with creatinine clearance less than or equal to 30 ml per min per 1.73 m2.
12.Patients with urinary outflow obstruction unless catheterized.
13.Patients with abnormal laboratory values at admission into the study: SGOT or SGPT more than 3 times the upper limit of normal or serum albumin less than or equal to 1.5 g/dl.
14.Prothrombin time greater than 22 sec or an international normalized ratio greater than 2.0 without anticoagulant therapy or 3.0 or more with therapy.
15.Patients taking CYP3A4 inhibitors or substrates such as ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, calcium channel blockers, digoxin or digitoxin, statins, benzodiazepines, vasopressin, oxytocin, desmopressin, carbamazepine, lithium, demeclocycline and urea.
16.Patients in whom another investigational drug defined as not approved for any indication by the local regulatory agency was used within 30 days of screening
17.Patients with any concurrent illness that could interfere with study treatment or its evaluation.
Mean change in the serum sodium level from baseline to end of study Clinical significance Mean change in serum sodium level more than 4 mEq per L Baseline serum sodium concentration refers to the mean of two serum sodium readings 0 and 4 hours obtained during the baseline period of 4 to 12 hours For the patients in whom treatment of hyponatremia with conivaptan cannot be delayed the sample at 0 hr will be considered as the baseline reading
Serum Sodium
Assessment 1 0 and 4 hr
Assessment 2 to 5 Morning and Evening
Percentage of patients with a more than 6mEq per L increase from baseline in serum sodium concentration or an increase to a normal serum sodium more than 135mEq per L level Baseline serum sodium concentration refers to the mean of two serum sodium readings 0 and 4 hours obtained during the baseline period of 4 to 12 hours. For the patients in whom treatment of hyponatremia with conivaptan cannot be delayed, the sample at 0 hr will be considered as the baseline reading
Serum Sodium Assessment 1 0 and 4 hr Assessment 2 to 5 Morning and Evening
This study is a multicentric, open label, non comparative, phase III study with a objective to assess the efficacy and safety of Conivaptan hydrochloride injection (administered as a loading dose of 20 mg for 30 min followed by the continuous intravenous of 20 mg for 24 hrs at assessment 2 and further based on the serum sodium readings administration of drug will be given as continuous intravenous infusion of 20 or 40 mg per day for an additional 1-3 days) in the treatment of euvolemic and hypervolemic hyponatremia. We have updated list of investigators, ethics committee approval status for version 3, inclusion and exclusion criteria, primary and secondary outcome