Desmopressin Reduces Bleeding Risk after Percutaneous Kidney Biopsy : A Randomized Controlled Study

Specific objectives (in bulleted form)

1. To evaluate whether desmopressin reduces the bleeding risk and severity after percutaneous kidney biopsy.

2. To evaluate weather administration of desmopressin in uremic patients increases FVIII, von Willebrand factor and platelet function.

3. To study safety profile of intra-nasal desmopressin.

Work plan methodology/experimental design to accomplish the stated aim including the sample size (Patient/Control/Volunteers) and source of volunteers/Control

STUDY DURATION - Total study duration will be 2 years, and patients will be recruited over the first 18 months of study. In last six months, lab investigation and data analysis will be carried out.

STUDY DESIGN - This study will be a double-blind, randomized, parallel group, placebo-controlled study.

STUDY SUBJECTS - All patients who will undergo renal biopsy in the above mentioned centre can be a part of study, subject to satisfaction of  inclusion and exclusion criteria; and willingness of the patient. Inclusion and exclusion criteria is mentioned below. Renal biopsy will be a part of institute protocol and evaluation of renal disease. No patient will undergo undue renal biopsy exclusively for study purpose. Indication for renal biopsy may be one of following: haematuria, proteinuria (nephrotic or sub-nephrotic range proteinuria) or unexplained renal failure.

RANDOMIZATION - All those patients who will fulfill the criteria for the study purpose they will be allocated into two different groups by computer-generated random number table in 1:1 ratio. Patient enrollment will be stratified into five group based on eGFR as per CKD staging (defined below in defination), with aiming at least 20 % in each group (1, 2, 3, 4 and 5).

BLINDING - All investigators, patients,  radiologist and data analyzer will be blinded.

DESCRIPTION OF INTERVENTION - Patients will be randomly assigned to the study drug desmopressin and placebo (normal saline). Allocation concealment will be done by sealed sequentially numbered opaque envelopes. They will be consecutively numbered, and medicine will be given out according to the number allocated to the participant. The investigator will be blinded to the allotment as the procedure will be carried out by a third person, a clinical coordinator employed for this purpose. Both the study drug and placebo will be given through intra-nasal route one hour prior to procedure. Drug (desmopressin or placebo) will be administered to patient by nursing staff not involved in study. Both the drugs, desmopressin and placebo (normal saline), will be provided as identical in appearance vials, and packing.

PROJECT IMPLEMENTATION PLAN:Patients will be screened to satisfy inclusion and exclusion criteria. Initial evaluation includes clinical history, measurement of height, weight, BMI, pulse rate, blood pressure, serum creatinine, complete blood count and clotting parameters. Patients will be randomly assigned to the study drug and placebo. Randomization will be done by computer-generated random number table on 1:1 ratio. Patient enrollment will be stratified into five group based on eGFR as per CKD staging (defined below in definition), with aiming at least 20 % in each group (1, 2, 3, 4 and 5). Both the investigators and patients will remain blinded for randomization until the end of the study. Both groups will continue antihypertensive medications and other treatments as before the study unless there is a specific contraindication. Both the study drug and placebo will be given through intra-nasal route two hours prior to renal biopsy. Renal biopsy will be performed by the nephrologist expert in the field. Ultrasound screening to look for evidence of bleeding will be done by experienced radiologist. About 4 ml blood will be collected in citrate vial (2 vials, 2 ml each) before administration of drug and 4 hour after.

FOLLOW UP AND MONITORING - After kidney biopsy, patients will be kept on strictly bed rest for 24 hour and follow up as per standard institute protocol. Vitals will be recorded immediately after procedure and every 30 minutes interval upto 2 hour then 6 hourly upto next 18 hours. Hemoglobin and hematocrit will be monitored at 0 hour (pre-biopsy), 4 hour and 24 hour. Serum creatinine will be done at baseline and as required by treating clinician. Screening ultrasonogram will be done immediately post biopsy and 24 hour after. In cases of post biopsy bleed, more frequent and prolonged monitoring will be done as per patients need. All drug related adverse effect will be recorded.

OUT COME - To compare the incidence of post biopsy bleed among two groups.